Natural Low Platelet Count Treatment Book

Conquer Low Platelets

Alternative And Natural Therapies For Itp (idiopathic Thrombocytopenia Purpura). Live Free From Itp. Complete Program To Increase Platelets. This Is What You Will Learn With this Guide: The Two Herbs That can help bring up your platelets. The Two Vitamins needed to keep those platelets from dropping. What foods may cause your platelets to drop. How science has confirmed the benefits of these herbs in their use with low platelets. Why your doctor may not know about these natural alternatives and how you can assist him in helping you. Different tests that naturopathic doctors do to determine your real state of health that may reverse the course of your body drastically. Understand some of the reasons why people develop low platelets. Discover how your digestive tract may be the culprit to your low platelet level problems. How you can prevent the most drastic step a splenectomy. How you can restore your health so that you dont need any more dangerous drugs. Get your life back and stop ending up in the hospital all the time. Learn why your immune system is attacking your platelets and how to calm it down. Learn what over the counter medications to stay away from if you have low platelets Read more...

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Heparin Induced Thrombocytopenia

HITS precludes the use of unfractionated heparin during PCI. Although the rate of HITS is less frequent with the LMWHs, cross-reactivity with these agents is observed and may be associated with increased rates of ischemic and bleeding complications. Whether pentasaccharides and hexadecasaccharides are safe and efficacious in this context has yet to be determined. The direct thrombin inhibitors are well suited to the management of HITS patients requiring PCI. Observational data for argatroban suggest that this agent can be safely used as an alternative to heparin in these patients. Case reports with recombinant hirudin (lepirudin) suggest that the use of this agent is also feasible.58 Similarly, a registry of 52 HITS patients receiving bivalirudin before PCI reported a 96 rate of freedom from death, Q-wave MI, and emergent CABG. Thrombocytopenia (platelet counts < 50 x 109 L) was not observed among these patients, suggesting that bivalirudin is also an alternative anticoagulation...

Heparininduced Thrombocytopenia

Approximately 2-3 of patients receiving unfractionated heparin for 5 or more days develop an immunologically mediated reaction, causing a relatively sudden decrease in platelet count to below 100 x 109 L1. It is caused by production of antibody to the heparin-platelet factor 4 complex on the surface of platelets (platelet factor 4 being a heparin-binding glycoprotein stored in platelet alpha granules). In a high proportion of cases, the resulting platelet activation leads to acute venous or arterial thrombosis and other events, including adrenal haemorrhagic infarction and skin necrosis at the sites of heparin injection. HIT also occurs in patients receiving prophylactic doses of heparin or LMWH but is much less common. The diagnosis should be suspected in a patient who has received heparin in any form for more than 4-5 days (or less if there has been previous exposure to heparin) and who has a relatively sudden decline in platelet count to less than 100 x 109 I r1 or to less than 50...


A beneficial effect of androgen therapy in thrombocytopenia due to marrow failure has been suggested by a study in myelodysplasia associated with thrombocytopenia in which 20 patients were randomised to receive either danazol (600 mg daily) or fluoxymesterone (1 mg kg day). Althoughboth groups had an impressive response in termination of clinical bleeding (6 6) and increasing platelet count (11 20), the lack of a placebo group means that the contribution of natural remission could not be evaluated (Wattel etal. 1994). The role of androgen therapy in immune thrombocytopenic purpura (ITP) remains poorly defined in the absence of controlled clinical trials. Two short-term observational studies have reported that danazol increases platelet counts in ITP as well as decreasing prednisone requirement (Ambriz et al. 1986) and reducing platelet-reactive IgG (Ahn etal. 1983).

Phosphodiesterase inhibitors

They are indicated for acute refractory cardiac failure, e.g. cardiogenic shock, or pre- or post-cardiac surgery. However, long-term treatment with oral PDE III inhibitors is associated with increased mortality in patients with congestive cardiac failure. All PDE III inhibitors may cause hypotension, and tachyarrhythmias may occur. Other adverse effects include nausea, vomiting and fever. Amrinone may cause thrombocytopenia and is available only as a parenteral preparation. The half-life of all PDE III inhibitors is prolonged several-fold in patients with cardiac or renal failure and they are commonly administered as an i.v. loading dose over 5 min with or without a subsequent i.v. infusion.

Replenishing Lost Volume

Coagulation disorders are both predisposing factors for, and consequences of, massive post-partum hemorrhage. A bleeding diathesis from a coagulopathy, thrombocytopenia or platelet dysfunction may result from pre-existing disease, a pregnancy-acquired disorder, such as eclampsia, or treatment, such as aspirin. Massive blood loss also creates both a coagulopathy and thrombocytopenia through dilution and consumption. These issues and their management are discussed in detail in Chapters 25 and 26.

Clinical Evidence of Direct Thrombin Inhibition

This class of agents, particularly bivalirudin, has emerged as a useful alternative to heparin as an anticoagulant among patients undergoing PCI as an adjunct and alternative to GP IIb IIIa inhibition. Early trials with hirudin focused on the prevention of restenosis in the setting of balloon angioplasty. Although no anti-restenotic effect was evident, reductions in early ischemic events were observed. These agents have found a role in the management of patients with heparin-induced thrombocytopenia (i.e., argatroban and bivalirudin), whereas most recent data suggest that improved thrombin inhibition with bivalirudin enables sparing of GP IIb IIIa inhibition in most patients undergoing PCI.

Clinical Evidence for Argatroban

For the widespread application to patients undergoing PCI, argatroban has not been studied in large-scale, randomized clinical trials. However, as an alternative to heparin among patients with heparin-induced thrombocytopenia syndrome (HITS), results of a small case series totaling 151 patients suggest that this agent is safe.40,41 Similarly, a small, non-blinded, uncontrolled study of argatroban administered to patients treated with abciximab (n 150) and eptifibatide (n 2) suggests that the combinations of these agents is at least feasible, but evidence defining the absolute benefits and risk associated with argatro-ban in the context of modern intervention practice is still lacking.42

Cobalamin Vitamin B12 and Folic Acid Deficiency

The hematologic picture is identical for both folate and vitamin B12 deficiency. Megaloblasts are enlarged blastic cells (precursors to the erythroid and myeloid cell lines) found in the bone marrow and caused by aberrant DNA synthesis. The peripheral blood smear typically shows the presence of oval macrocytes, hypersegmented neutrophils (> 5 neutrophils with 5 lobes or any neutrophil with 6 lobes). Anisocytosis (size variation) and poikilocytosis (shape variation) of the red blood cells (RBCs) are often present, so the RBC distribution width (RDW) is increased. The reticulocyte count is usually decreased. Thrombocytopenia is present in 12 and leukope-nia in 9 of cases occasionally, B12 or folate deficiency will present with pancytopenia. Coexisting disease such as iron deficiency, inflammatory process, renal failure, or thalassemia trait also may normalize the mean corpuscular volume (MCV) value in the patient with vitamin B12 or folate deficiency.

Mononucleosis Epstein Barr Virus Infection

Typically, mononucleosis is associated with an infection by the Epstein-Barr virus (EBV), which is a herpesvirus. Laboratory findings include leukocytosis, with more than half the leukocytes being lymphocytes. Approximately 10 to 15 of the mononuclear cells are atypical lymphocytes. Thrombocytopenia may develop with infectious mononu-cleosis. Almost 90 of patients with mononucleosis have abnormal liver enzymes. Mononucleosis is typically diagnosed by detecting a heterophile antibody, which is a nonspecific response to EBV infection. The heterophile antibody response is an IgM antibody that will agglutinate with the surface antigen of sheep and horse RBCs, but not with guinea pig kidney cells. Monospot tests are done with rapid slide agglutination procedures and horse RBCs to detect the heterophile antibody. Clinically, about 40 of patients have a positive heterophile antibody response at week 1, 60 at week 2, and 80 to 90 by week 3. The heterophile antibody usually persists for 3 to 6...

Direct Thrombin Inhibitors

Transfusions was observed in the streptokinase plus bivalirudin group. Bivalirudin, as an alternative to unfractionated heparin, may be acceptable (class IIa recommendation) in patients with heparin-induced thrombocytopenia and STEMI treated with streptoki-nase based on the HERO-2 trial.

Anticoagulant Therapy During Pregnancy And The Peripartum Period

Epidural anesthesia is generally safe in women following discontinuation of UFH, providing their coagulation screen is normal and their platelet count is > 80 x 109 l. It remains unclear what period of time should elapse between the last dose of LMWH and insertion or removal of an epidural or spinal catheter, or how long the time interval should be until the next dose. In practice, it is reasonable to allow at least 12 h to elapse after a prophylactic dose of LMWH before inserting an epidural or spinal catheter, but a delay up to 24 h may be necessary in patients on therapeutic doses of LMWH. At least 2 h should elapse after insertion of the catheter before LMWH is given again. If there have been difficulties with the procedure, then it is prudent to delay prior to giving further prophylaxis.

Antiphospholipid Antibodyinduced Pregnancy Loss

The anti-phospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis and thrombocytopenia occurring in the presence of anti-phospholipid (aPL) antibodies. Pregnancy loss is a defining criterion for APS and occurs with particularly high frequency in systemic lupus erythematosus (SLE) patients bearing this antibody.

Monitoring The Clinical Effect Of rFVIIa

Coagulopathy is usually easy to recognize by the clinical assessment of ongoing bleeding, physical examination and observation of oozing from cut surfaces, intravascular catheter sites or mucus membranes. The initial evaluation during hemorrhage includes the PT, APTT, thrombin time (TT) and fibrinogen concentration, antithrombin and platelet count. In the interpretation of these tests, it is important to know the normal range and to be aware of the sensitivity of the screening tests for each coagulation factor, as these vary from laboratory to laboratory. In addition, assays of clotting parameters may provide different results with different reagents, although these parameters do not show a direct correlation to the level of hemostasis achieved. Finally, it is important to remember that laboratory coagulation parameters may be used as an adjunct to the clinical evaluation of hemostasis for monitoring the effectiveness and treatment schedule of rFVIIa34.

Technical Aspects Preparation

Unless it is an absolute emergency, obtaining a coagulation panel including the platelet count, APTT and PT (INR) is worthwhile (see Chapter 25). Deranged coagulation does not necessarily contraindicate arteriography or embolotherapy7 however, its correction may help in preparation for post-procedural hemostasis and the prevention of complications relating to this. Occult coagulopathy may also be revealed8. As emboli-zation is an invasive procedure, informed consent from the patient is essential, with explanation and discussion of the possible complications, future fertility and the effects of the radiation. In situations where the patient is sedated or unable to consent, the appropriate consenting process should be considered. Ideally, the patient is kept nil by mouth for an appropriate duration prior to procedure in order to avoid complications from vomiting. Bladder catheter-ization is not essential, although it is helpful in preventing the bladder from filling with...

Maternal Substance Abuse

The risks of regional anesthesia are increased in cocaine-abusing parturients. Cocaine abuse is associated with thrombocytopenia421 therefore, the platelet count should be determined before initiating neuraxial analgesia or anesthesia. After neuraxial blockade, the degree of hypotension is more profound.14231 Because ephedrine is both an indirect- and direct-acting vasopressor, it is less effective in treating hypotension in the cocaine-positive parturient.823 Finally, cocaine-abusing parturients often experience pain despite apparently adequate regional anesthesia. Regional analgesic or anesthetic techniques may be advantageous for the opioid addict because analgesia can be provided without opioids. Autoimmune thrombocytopenia has been reported in opioid abusers.1433 As with cocaine abuse, apparently adequate regional anesthesia may not provide acceptable pain relief in some opioid users.

Laboratory Abnormalities

In active SLE, serum complement (C3, C4, and often CH50) levels are depressed. ESR is often elevated during active disease but is not a precise indicator of disease activity. DNA autoantibodies also do not correlate well with periods of active disease. A normochromic normocytic anemia, leu-kopenia (2500-4000 WBCs mm3), and thrombocytopenia are common because of bone marrow suppression or the autoimmune process, although other causes must be ruled out first. SLE can manifest as immune thrombocytic purpura years before the patient develops other symptoms of lupus.

Intravenous Thrombolysis

Threefold increase in good outcome this dropped to 1.6-fold for patients treated between 91 and 180 minutes after stroke onset. For those treated between 180 and 270 minutes, the odds ratio for benefit was 1.4 times greater than placebo. The risk of ICH was greater for the thrombolytic group (5.9 ) compared with the placebo group (1.1 ), but most of these hemorrhages were asymptomatic. The number of stroke patients needed to treat (NNT) with IV lysis in order to achieve an excellent outcome and avoid 1 stroke death or dependency was 7. For every 100 stroke patients treated with IV thrombolysis within 3 hours after stroke onset, 32 had a better outcome, although 3 experienced a significant ICH. At 1 year after treatment, those treated with IV lysis had a 30 increased likelihood of minimal or no disability compared with placebo however, there was no difference in mortality, and the rate of recurrent stroke was not different.9 The risk of hemorrhage was increased in elderly patients and...

The patient interview

History of definite systemic inflammatory disorder, or suggestive clinical features such as photosensitivity, arthritis, pericarditis, pleuritis, repetitive spontaneous miscarriage, oral or genital aphthosis, unexplained fever, anemia, thrombopenia, proteinuria (in favor of cerebral vasculitis)

Myeloproliferative Disorders

In ET the peripheral smear reveals increased numbers of platelets of various sizes. Platelet counts may be high, in excess of 1 or 2 x 106 L. There may be an associated leukocytosis, and Hb level is typically normal. The decision to treat such patients is not always easy. Generally, patients with platelet count approaching 1 x 106 L are treated, even with no associated symptoms or signs. Asymptomatic young women with ET require special consideration watchful waiting is probably sufficient, although hydroxyurea plus aspirin is the most effective approach for patients who require treatment. Patients with AMM MF tend to run an indolent course. Usually, over time, the spleen continues to enlarge, and peripheral RBC destruction increases. There also may be varying degrees of thrombocytopenia caused by impaired bone marrow production and increased splenic sequestration. In all the myeloproliferative disorders, platelet function may be abnormal. Treatment of AMM MF is largely symptomatic....

Primary Insufficiency

AIDS patients are at risk for adrenal insufficiency from multiple causes. AIDS patients' adrenal glands may be infiltrated by multiple infections and malignant processes, including cytomegalovirus, Mycobacterium tuberculosis or M. avium-intracellulare, Pneumocystis carinii, toxoplasmosis, histoplasmosis, Kaposi's sarcoma, and lymphoma. The human immunodeficiency virus may invade the adrenal. The adrenal is the preferred site of cytomegalovirus in the AIDS patient.9 Autoimmune adrenalitis also occurs. Drugs used in the treatment of AIDS-related diseases such as ketocona-zole, corticosteroids, rifampin, and phenytoin may also contribute to impaired adrenal function. Thrombocytopenia may lead to acute adrenal hemorrhage. The severe hypocho-lesterolemia seen in some AIDS patients may lead to impaired corticosteroid production.10

Emergency Department Treatment and Disposition

The emergency physician's efforts are initially focused on stabilization of the patient with two large intravenous lines, type and cross-match, and crystalloid infusion if significant bleeding has occurred. Because of the complexity of the differential diagnosis and potentially complicated treatment of HIV thrombocytopenia, an infectious disease specialist should be consulted early. In most cases, HIV patients with platelet count greater than 50,000 can be managed conservatively with spontaneous remission of approximately 20 . Zidovudine can increase platelet counts up to two-fold in over 50 of patients. If the platelet count is less than 20,000, many infectious disease specialists recommend -globulin infusion and parenteral steroids. Other possible treatments include dapsone, danazol, interferon-a vincristine, anti-D immunoglobulin, splenic irradiation, and splenectomy. Even if the patient is to be managed conservatively, bone marrow analysis should be performed to rule out other...

Antithrombin Aptamer ARC183

Heparin has been used extensively, and almost exclusively, as the anticoagulant during cardiac surgery, including CABG procedures. The reasons for its use are related to low cost, ease of monitoring (by activated clotting time (ACT)), reversibility (using protamine) and lack of a suitable anticoagulant replacement. There are, however, several limitations to the use of heparin, including a long halflife requiring protamine to be used as an antidote heparin-induced thrombocytopenia in 2-5 of patients exposed significant non-specific plasma binding he-parin cannot inhibit clot bound thrombin and heparin has been associated with platelet aggregation and dysfunction (Warkentin and Greinacher, 2003 Adler, 2004). Moreover, protamine has been associated with immune-mediated reactions, and its short half-life ( 5 min) may result in unopposed heparin effects post operatively (Butterworth et al., 2002). The adverse properties and limitations of heparin with protamine illustrate that this...

Immunological Abnormalities

Circulating antibodies, like lupus anticoagulant (LA) and anticardiolipin antibodies, may be related to stroke. The LA is a phospholipid antibody that interferes with the formation of the prothrombin activator. In the laboratory, there is a prolonged activated partial thromboplastin time (PTT). Some patients with LA have SLE, but most do not. When antiphospholipids of the IgG, IgM, or IgA classes are found in the absence of a known systemic illness, and patients present with an increased incidence of spontaneous abortions, thrombophlebitis, pulmonary embolism, and large- and small-artery occlusions, the disorder is now referred to as primary antiphospholipid lupus anticoagulant (APLA) syndrome. The APLA-associated stroke syndrome is characterized by its younger age at onset, predominance in women, and high risk of recurrent thrombo-occlusive events. Some patients have mitral and aortic valve vegetations and ocular ischemia. In addition to the presence of LA or anticardiolipins, or...

Initial Diagnostic Evaluation of a First Seizure in Adults

A careful history and physical examination, along with routine blood work, can detect many medical problems that may be associated with seizures. Such problems include infection, electrolyte and glucose abnormalities, impaired hepatic or renal function, and cardiopulmonary disease. Most patients with new-onset seizures should have a CBC with platelet count and differential, toxicology screen, thyroid function testing, PT PTT, determination of serum transaminase, electrolyte, calcium, magnesium, phosphorus, BUN, creatinine, glucose, ABGs, or pulse oximetry. If cardiopulmonary disease is suspected, ECG and chest radiograph should be obtained. Meningitis or encephalitis suspected clinically indicates LP, which is otherwise not necessary. Patients usually recover rapidly after a first seizure, and their clinical progress can be gauged after several hours of observation. Hospitaliza-tion is not usually necessary after a first seizure unless an underlying illness is suspected or there are...

Bacterial Meningitis

Toxic effects tremor, thrombocytopenia Hyponatremia, hypersensitivity reaction, leukopenia, thrombocytopenia, angioedema, Stevens-Johnson syndrome, dizziness, somnolence, diplopia, headache, nausea, ataxia Thrombocytopenia, hypersensitivity reaction, angioedema, dizziness, somnolence, ataxia, peripheral edema, weight gain Additional laboratory studies include CBC, platelet count, PT, PTT, ABGs, and determination of electrolyte, protein, glucose, BUN, and creatinine levels. Further laboratory workup and imaging studies (chest film, sinus series, skull films) may be indicated, depending on the clinical setting.

Multicenter Registry Experience

The risk of bleeding from the pericardiotomy site appears to be increased in patients with platelet or coagulation abnormalities. For this reason, we do not recommend performing PBP on patients with uremic pericardial effusions or when coagulation parameters cannot be normalized (refractory coagulopathy or thrombocytopenia). In those patients at high risk for bleeding, a surgical procedure under direct visualization may be safer.

Coagulation Disorders

In general, the commonly recommended tests include the prothrombin time, the partial thromboplastin time, a complete blood cell count with platelet count, and in some patients, a bleeding time. The platelet count identifies numbers of platelets, whereas the bleeding time estimates qualitative platelet function. None of the commonly recommended screening tests measures fibrinolytic function. Additional screening tests that may be used for specific patients include a fibrinogen level, the thrombin time, and screens for factor XIII levels. The thrombin time detects abnormalities of globulin, fibrinogen, excess fibrinolysis, and heparin-like substances. In patients suspected of having platelet dysfunction, additional assessments include platelet function tests (aggregation with epinephrine, adenosine diphosphate, collagen, and ristocetin). If a deficiency or specific factor is suspected, as in patients with a family history of hemophilia, then specific factor assays should be obtained (8).

Haematolofjical system

Platelet and coagulation disorders may occur as discussed above. A rapidly decreasing platelet count is indicative of a worsening of pre eclampsia, and low platelets may be associated with HELLP syndrome (haemolysis, elevated liver enzymes and low platelets). In general, a platelet count of 100 x 10 L 1 (taken within the last 12 h) and above is safe for insertion of an epidural catheter. At levels below this, a clotting screen is advised and the risks and benefits of regional block should be assessed.

Vasculitis Associated with Antiphospholipid Antibodies

Antiphospholipid antibodies (aPL) are a heterogenous family of antibodies of the IgG, IgM, or mixed classes with varying cross- reactivities. Antibodies within this family include anticardiolipin antibodies, antibodies responsible for the false- positive Venereal Disease Research Laboratory (VDRL) serology and the lupus anticoagulant. Antiphospholipid antibodies may be detected in a number of clinical settings. Normal elderly may have aPL of unclear significance. They may be seen in patients treated with phenothiazines, antiarrhythmics, and anticonvulsants, or in the context of infections or malignancy. Antiphospholipid antibodies are commonly seen in patients with systemic autoimmune disorders such as systemic lupus erythematosus. The primary antiphospholipid antibody syndrome comprises recurrent venous or arterial thrombosis, fetal loss, thrombocytopenia and positive results on serological tests for lupus anticoagulant or anticardiolipid antibodies....

RIT in Follicular Lymphoma

In the initial Phase I II study, 90Y-Ibritumomab was administered on 51 patients with relapsed and refractory CD20+ B-cell non-Hodgkin's lymphoma (Witzig, White, Wiseman, Gordon, Emmanouilides, Raubitschek, Janakiraman, Gutheil, Schilder, Spies, Silverman, Parker and Grillo-Lopez 1999). The overall response rate (ORR) for the 34 patients with indolent lymphoma was 82 percent (complete response (CR) 26 and partial response (PR) 56 ). The estimated median time to progression (TTP) for the entire group was 12.9+ months and the median duration of response was 11.7+ months. The major toxicity of 90Y-ibritumomab was myelo-suppression with thrombocytopenia being the most common. 90Y-ibritumomab has been compared to rituximab in a randomized controlled Phase III study (Witzig, Gordon, Cabanillas, Czuczman, Emmanouilides, Joyce, Pohlman, Bartlett, Wiseman, Padre, Grillo-Lopez, Multany and White 2002). The ORR was 80 percent (CR CRu 34 and PR 45 ) for 90Y-Ibritumomab, as compared to 56 percent...

Epidemiology And Etiology

For an allogeneic HSCT, the recipient and the donor are dissimilar genetically unless they are identical twins (a transplant between twins is referred to as a syngeneic HSCT). The transplanted tissue is immunologically active, and thus there is potential for bidirectional graft rejection. In the first scenario, cytotoxic T cells and natural killer (NK) cells belonging to the host (recipient) recognize minor histocompatibility (MHC) antigens of the graft (donor hematopoietic stem cells) and lead to a rejection response. In the second scenario, immunologically active cells in the graft recognize host MHC antigens and elicit an immune response. The former is referred to as host-versus-graft disease and the latter is referred to as GVHD. Host-versus-graft effects are more common in solid-organ transplantation. When host-versus-graft effects occur in allogeneic HSCT, they are referred to as graft failure or rejection, which results in ineffective hematopoiesis (i.e., adequate ANC and or...

Colony Stimulating Factors

Although generally well tolerated, CSFs may cause bone pain in around 25 of patients. This may be managed with acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs), although attention to the platelet count is warranted with the use of NSAIDs. Sargramostim in particular may result in low-grade fever and myalgias, perhaps as a result of its wider pattern of effector cell stimulation.

Clinical Use and Adverse Effects of Specific Antiepileptic Drugs

Valproic acid is a branched-chain fatty acid that was approved for use in the United States in 1978. The enteric-coated preparation, divalproex sodium, became available in 1983. Multiple mechanisms likely contribute to its broad spectrum of action, including inhibition of sustained repetitive firing through blockade of voltage-gated Na+ channels. Valproic acid is effective against generalized and partial seizures including absence, myoclonic, and tonic-clonic seizures. High protein binding and hepatic enzyme inhibition contribute to the high incidence of drug interactions. Adverse reactions include tremor, weight gain, alopecia, hyperammonemia, carnitine deficiency, and thrombocytopenia. Fulminant hepatic failure and fatal pancreatitis have been reported. Valproate is available in 250-mg tablets and syrup (250 mg 5 ml), and divalproex sodium in 125-, 250-, and 500-mg tablets and 125-mg sprinkles for mixture with food. Rectal and parenteral formulations are being developed.

Congenital platelet disorders

Minor trauma menorrhagia is a common presentation. Laboratory findings include thrombocytopenia, large platelets, prolonged bleeding time and poor platelet aggregation in vitro to ristocetin. Glanzmann's thrombasthenia is due to a spectrum of mutations in platelet membrane GP IIb IIIa, resulting in failure to bind fibrinogen. It is characterized by excessive menstrual blood loss, bleeding from mucous membranes, and major hemorrhage following trauma or surgery. The platelet count is normal, but clot retraction is greatly impaired and agents such as adenosine diphosphate (ADP), epi-nephrine and collagen fail to induce platelet aggregation. Patients with this condition are at increased risk of primary postpartum hemorrhage. Single-donor platelets (again, HLA-matched if possible) and recombinant activated FVII have been used to control bleeding during the peripartum and the postpartum period61. The May-Hegglin anomaly is a rare autosomal dominant condition with thrombo-cytopenia and giant...

Abnormal clotting increased bleeding tendency

Platelet count is measured routinely as part of a full blood count. A normal value is 150-400 x 10'' per litre. Bleeding is rarely a problem when the platelet count is above 50. Severe or spontaneous bleeding occurs with values below 20. There are multiple causes of thrombocytopenia, which can be broadly divided into those with excessive loss or consumption of platelets and those with impaired production. Either form can be congenital or acquired. Important examples are discussed below. This condition is also known as autoimmune thrombocytopenic purpura and the platelet count might be undetectable. Treatment of thrombocytopenia is directed at the underlying cause (e.g. ITP might respond to steroid therapy or splenectomy). During surgery, if a patient is actively bleeding with a low platelet count, platelet transfusion can provide a temporary solution. However, these transfusions are prone to the same fate as the patient's endogenous platelets (e.g....

Acute Adrenal Insufficiency Related to Bilateral Adrenal Hemorrhage

Veins Fragile Adrenal

Although historically bilateral adrenal hemorrhage is associated with meningococcemia in children (Waterhouse-Friderichsen syndrome), bilateral adrenal insufficiency occurs most commonly in adults in association with anticoagulant therapy. Clinical conditions producing coagulopathies such as thrombocytopenia, anticardiolipin antibody, and lupus anticoagulant also result in bilateral adrenal hemorrhage. Trauma, either directly or through the destruction of the blood supply to the adrenal, may result in bilateral adrenal hemorrhage. Septicemia, although more commonly a cause of adrenal hemorrhage in children, may lead to adrenal hemorrhage in adults. Stress associated with illness, sepsis, or burns may lead to bilateral adrenal hemorrhage. Because of the rapidly fatal outcome of bilateral adrenal hemorrhage, the surgeon must suspect this clinical entity in these settings. Although therapeutic anticoagulation with heparin or warfarin is the factor most commonly implicated in bilateral...

Patient Care and Monitoring

In a patient presenting with a bleeding or clotting disorder, an initial evaluation should include bleeding time, prothrombin time (PT), activated partial throm-boplastin time (aPTT), thrombin time, and platelet count. Bleeding time indicates how well platelets interact with blood vessel walls to form blood clots by assessing the length of time to arrest the bleeding after a standardized skin cut. The bleeding time is prolonged in thrombocytopenia, fibrinogen disorders, and collagen defects. Monitor platelet counts, hemoglobin, and LDH.

Pharmacologic Therapy Chemotherapy

Nausea, neuropathy. peripheral neuritis, vomiting, thrombocytopenia, thrombotic events, bleeding, and proteinuria Febrile neutropenia infection, thrombocytopenia, nausea, vomiting, diarrhea. High (day 2 only) cardiac toxicity, renal toxicity, neuropathy, weakness. hypersensitivity reactions, and anemia Infection, thrombocytopenia, nausea, vomiting, diarrhea, cardiac, renal. Wgh (day 1 only) neuropathy, wakness. hypersensitivity, and anemia Febrile neutropenia infection, thrombocytopenia, and nausea, vomiting, diarrhea, rtgh (day Ik mild infusion reactons. and hypomagnesemia Neutropenia, infection.anorexia, thrombocytopenia, nausea, vomiting.dyspnea, tfigh (day I and 8) ccnstipaton. icutcpathy. and anemia infection, thrombocytopenia. nausea, vomiting, diarrhea, cardiac, renal. High (day I only) neuropathy, weakness, hypersensitivity, and anemia AJopecia. nausea and vomiting, neurotoxicity, and thrombocytopenia Moderate Nausea and vomiting, diarrhea, thrombocytopenia, asthenia, and...

A 9substituted camptothecins

All of the studies report neutropenia as the DLT, while thrombocytopenia is also frequent and sometimes severe. Gastrointestinal toxicity is the second most reported, though not dose limiting. Other toxicities are considered mild to moderate. Numerous multi-institutional Phase II studies have been conducted in several disease types, and overall, 9-AC shows only very modest singleagent activity with the prolonged (72- or 120-h infusion) regimens. These include trials in breast cancer (268), colorectal cancer (269-272), glioblastoma (273), head and neck cancer (274), lymphoma (275,276), and NSCLC (277,278). Therefore, its further evaluation does not seem to be indicated. It has been suggested that the lack of clinically relevant antitumor efficacy relates to substantial inactivation of the agent due to the unfavorable lactone carboxylate ratio in patients (279,280). In addition, using preclinical studies it has been shown that solid-tumor xenografts were highly sensitive to 9-AC...

Factor VII deficiency

Thrombocytopenia in pregnancy differential diagnosis, pathogenesis and management. Blood Rev 2003 17 7-14 7. McCrae KR, Samuels P, Schreiber AD. Pregnancy-associated thrombocytopenia patho-genesis and management. Blood 1992 80 2697-714 8. Shehata N, Burrows RF, Kelton JG. Gestational thrombocytopenia. Clin Obstet Gynecol 1999 42 327-34 11. Burrows RF, Kelton JG. Thrombocytopenia during pregnancy. In Greer IA, Turpie AG, Forbes CD, eds. Haemostasis and Thrombosis in Obstetrics and Gynaecology. London Chapman & Hall, 1992 14. Letsky EA, Greaves M. Guidelines on the investigation and management of thrombocyto-penia in pregnancy and neonatal alloimmune thrombocytopenia. Maternal and Neonatal Haemostasis Working Party of the Haemostasis and Thrombosis Task Force of the British Society for Haematology. Br J Haematol 1996 95 21-6 15. Crowther MA, Burrows RF, Ginsberg J, Kelton JG. Thrombocytopenia in pregnancy diagnosis, pathogenesis and management. Blood Rev 1996 10 8-16 17....

Disseminated Intravascular Coagulation

The principal laboratory findings are produced by the consumption of platelets during intravascular coagulation with reduction of fibrinogen and elevation of FDP in the serum as secondary (physiological) fibrinolysis breaks down thrombus. Thrombocytopenia, hypofibrinogenaemia and elevation of serum FDP are thus the hallmarks of DIC. Scrutiny of the blood film may reveal red cell distortion or fragmentation if there is associated microangiopathy. have more profound thrombocytopenia. There is some suggestion that in severe DIC, there is, in addition, an induced platelet function defect. DIC is inevitable to some degree where there is tissue damage (particularly the brain), hypotension, shock and poor organ perfusion. Variants of the syndrome (with similar laboratory findings) may occur with localized extravascular consumption (e.g. placental abruption) and localized intravascular consumption (e.g. aortic aneurysm). Occasionally, primary pathological fibrinolysis (PF) occurs without the...

Ascites In Pathophysiology In Book

Portal Hypertension Ascites

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patients. Splenic sequestration secondary to splenomegaly is one of the causes of thrombocytopenia in cirrhotic patients. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the rennin- clotting times (e.g., prothrombin time) and bleeding irregularities. Thrombocytopenia is another coagulation abnormality seen in advanced liver disease. This is a result of decreased platelet production in the bone marrow (triggered by a lack of throm-bopoietin stimulation by the liver) as well as the splenic sequestration of formed platelets. Macrocytic anemia may also occur because of decreased intake,...

Pharmacological Agents Nifedipine

Amiodarone Blue Skin

Heparin-induced skin necrosis may be seen in the arms and is attributed to hypersensitivity angiitis (127). Bleeding into the skin or mucous linings is readily detected if the heparin dose is excessive or in the rare instance of heparin-induced thrombocytopenia (128) (Fig. 14). Fig. 14. Heparin-induced thrombocytopenia 80-yr-old female who developed an extensive area of ecchymosis over the anterior chest wall and severe thrombocytopenia. Four days previously she had received (direct current) DC shock for ventricular tachycardia as well as heparin for an acute myocardial infarction. She had received heparin for a deep vein thrombosis in the past without any ill effects. Fig. 14. Heparin-induced thrombocytopenia 80-yr-old female who developed an extensive area of ecchymosis over the anterior chest wall and severe thrombocytopenia. Four days previously she had received (direct current) DC shock for ventricular tachycardia as well as heparin for an acute myocardial infarction. She had...

Pathophysiology Of Mods

After the initial insult (induced by physical, biological or chemical injury) there is a local inflammatory response at the site of injury or infection. If the injured and or hypoxic microenvironment cannot control the initial insult, there is an accentuated inflammatory response. If the impact of the injury is too extensive (e.g. during polytrauma, after major surgery, etc.) or if the host's immune system is weakened (e.g. advanced age, drug induced immunosuppression, etc.), there may occur a systemic inflammatory response (SIRS) resulting in excessive activation of the complement and cellular defense systems. Furthermore, there may also follow a dysregulation of the coagulation cascade and profound dysfunction of the endothelium with persistent vasodilatation. At this stage, clinical signs of MODS appear, as reflected by lung dysfunction (impairment of arterial oxygenation), renal dysfunction (azotemia, oliguria), liver dysfunction (increasing transaminases with hyperbilirubinemia),...

Evaluation Guidelines

A basic workup that should be performed in all patients with ischemic stroke includes a complete blood count with differential and platelet count, erythrocyte sedimentation rate, prothrombin time with International Normalized Ratio (INR), partial thromboplastin time, plasma glucose level, blood urea nitrogen, serum creatinine, lipid analysis, luetic serology, and urinalysis (see Iab e.22I3. ). A basic evaluation that should be performed in all patients with intracerebral hemorrhage includes a complete blood count with differential and platelet count, prothrombin time with partial thromboplastin time, erythrocyte sedimentation rate, plasma glucose, serum alkaline phosphatase, serum glutamic oxalate transaminase, serum calcium, blood urea nitrogen, serum creatinine, and urinalysis. Additional paraclinical evaluation is listedin iTab, e, 22-3 .

Patient Encounter 2 Part 3 ITP Creating a Care Plan for ITP patient

For most patients, the initial dose of eltrombopag is 50 mg once daily. The daily dose is subsequently adjusted to a maximum dose of 75 mg daily, in order to achieve and maintain a platelet count greater than or equal to 50 x 103 mm3 (50 x 109 L) in order to reduce the risk for bleeding. Romiplostim and eltrombopag are effective in increasing platelet counts in patients with ITP and can be used in combination with therapies that inhibit platelet destruction. While usually well tolerated, a number of rare but serious risks have been reported, including changes in the bone marrow, worsened thrombocytopenia and the risk of bleeding after cessation of the medication, thrombotic thromboembolic complications, and worsening of blood cancers. Eltrombopag carries a black-box warning regarding hepatic toxicity. It is also associated with development of cataracts and has multiple drug-drug interactions. To enhance patient safety, both romiplostim and eltrombopag are available only through...

Acquired And Congenital Hemostatic Disorders In Pregnancy And The Puerperium

Thrombocytopenia Thrombocytopenia is the most common hemo-static abnormality and may complicate up to 10 of all pregnancies. The normal platelet count ranges from 150 to 400 x 109 l, and thrombocytopenia is defined as a count of less than 150 x 109 l. The platelet count may decline by approximately 10 during normal pregnancy6. Spontaneous bleeding is unusual unless the count has fallen to below 30 x 109 l, but surgical bleeding or postpartum hemorrhage may occur as a consequence of platelets less than 50 x 109 l. Thrombocytopenia in pregnancy may result from variety of causes (Table 2). The timing of onset of these disorders during pregnancy and their clinical manifestations often overlap, making the identification of individual causes of thrombocytopenia sometimes problematic. It is important to consider spurious thrombo-cytopenia as a possible cause of decreased platelet count before embarking on extensive investigations or treatment. This is a laboratory artefact due to...

Von Willebrand disease

DDAVP, a synthetic vasopressin analogue, releases vWF from endothelial stores there is also an increase in the plasma FVIII level. It is usually given by slow intravenous infusion of 0.3 lg kg over 20 min, which can be repeated every 4-6 h on two or three occasions. The drug can also be given subcutaneously or as a nasal spray. Side-effects include hypotension, facial flushing, fluid retention for up to 24 h and consequent hyponatremia. DDAVP can safely be used during pregnancy66 and after delivery. It is effective in securing in many situations in type 1 vWD with a 3-5-fold increase in the plasma vWF and FVIII levels. It is of no therapeutic benefit in type 3 vWD because of the very low basal levels of vWF and FVIII. The response in types 2 is less predictable. DDAVP is contrain-dicated in patients with type 2B because it may exacerbate the coexisting thrombocytopenia. Patients should have a test of DDAVP (if possible when not pregnant) to see if it is effective in their individual...

Evaluation Guidelines Table82

Blood studies are indicated when specific pathological processes are suspected. Vascular events may require evaluation of the erythrocyte sedimentation rate (ESR), rapid plasmin reagin (RPR), antinuclear antibody (ANA), and coagulation indices such as prothrombin time, partial thromboplastin time (PT and PTT), and platelet count. The ESR is especially important in transient or permanent visual loss in the elderly to rule out giant cell arteritis. In young individuals without an obvious risk factor for stroke, protein C, protein S, antithrombin III, antiphospholipid antibody, and anticardiolipin antibody levels should be obtained. A toxicology screen is necessary if drug use is suspected. Most intracranial mass lesions require either at least brain biopsy if a primary neoplasm is suspected, or a metastatic evaluation if multiple metastases are more likely. In many cases of demyelinating disease, other autoimmune, inflammatory,

Rocky Mountain Spotted Fever

The classic rash of Rocky Mountain spotted fever first appears as macules on the wrists and ankles and subsequently spreads to involve the trunk, face, palms, and soles. The rash appears 1 to 15 days after the onset of the illness. w The rash is initially a diffuse erythematous maculopapular rash that blanches with pressure. It progresses to a petechial rash, then to a purpuric rash, and if untreated, to skin necrosis or gangrene. The rash begins on the wrists and ankles and then spreads distally and proximally within a few hours. Ten percent of patients do not have a rash (spotless Rocky Mountain spotted fever). Neurological manifestations of Rocky Mountain spotted fever include severe bifrontal headache that is unresponsive to common analgesics, delirium, confusion, seizures, coma, hyperreflexia, spastic paraparesis or quadraparesis, facial diplegia, nystagmus, and or ataxia. Stupor and coma occur in approximately 25 percent of patients and are associated with a poorer prognosis...

Mouth or Throat Sores

Brush the teeth with a soft nylon bristle toothbrush only. To soften the bristles even more, use hot water on the bristles before and after use. If toothpaste is irritating, try a paste composed of baking soda and water. If brushing hurts too much, clean teeth with cotton swabs or commercial sponge-tipped sticks called Toothettes. Floss with unwaxed dental floss avoid flossing if there are bleeding problems or if platelet count is low. Using a Waterpik can help keep the mouth clean, too.

Eosinophilic Myositis and Related Syndromes

Eosinophilic fasciitis often will improve spontaneously, but resolution is faster with corticosteroid treatment. Relapses are infrequent. Although the treatment and resolution are in most cases good, the acute phase of the illness can be complicated by aplastic anemia, and either amegakaryocytic or idiopathic thrombocytopenia. Delayed lymphoproliferative disorders have also occurred. W

Blood Products Acceptable For Jw

Recombinant coagulation factor VIIa (rFVIIa Eptacog-alfa Novoseven Novo-Nordisk) is licensed for treatment of hemophilia patients with inhibitors and for congenital disorders of platelet function14,15. The drug is also being used (off-license) to treat life-threatening hemorrhage in non-hemophilic patients16. In the setting of severe thrombocytopenia, if the thrombocytopenia is due to decreased production of platelets (as in leukemia and other bone marrow failures), it is anticipated that rFVIIa would be ineffective because rFVIIa needs access to platelet surfaces to prevent bleeding. In autoimmune thrombocytopenia, however, a low platelet count is hemostatically more effective as the platelets are younger and have more membrane surface, making it more responsive

Clinical Manifestations and Pathology

Common laboratory findings in 29 patients admitted to hospitals were low white blood cell count, relative lymphocytosis (71 percent), and a reduced platelet count. All four dengue serotypes were isolated (12 cases of dengue 1, 4 cases of dengue 2, 5 of dengue 3, and 1 of dengue 4). All patients survived their illness and returned to normal health. This outbreak of mixed classical benign dengue fever and dengue hemorrhagic fever of multiple serotype is typical of current dengue epidemics. Severe dengue disease - dengue hemorrhagic fever and dengue shock syndrome - proceeds through two stages. The first is similar to that of benign dengue however, patients deteriorate during or shortly after the fall in temperature. If hypovolemic shock supervenes (because of a greatly reduced volume of plasma), untreated patients may expire within 6 hours. The clinical evidence of disturbances of blood coagulation is accompanied by abnormal laboratory tests. Hemoconcentration and reduced platelet count...

B dosefinding trials

Secondly, various schedules focusing on the continuous infusion of topotecan have been studied, including a 24-h infusion weekly, and every 3 weeks, a 72-h infusion administered weekly, every 14 days and every 21 days, a 120-h infusion every 3-4 weeks, and 21-day low-dose continuous infusion every 4 weeks (27). In addition to the DLT of leucocytopenia, the longest infusion schedules also induce thrombocytopenia.

Prevention Of Deleterious Effects

Other complications include infection or epidural hematoma. Care must be taken to prevent contamination of the catheter by avoiding puncture near a site of active infection, protecting the puncture site with sterile dressings, frequently inspecting and redressing the site for long-term maintenance. Epidural hematomas can be prevented by avoiding the use of epidural catheters in patients with clotting abnormalities, such as severe liver disease, uremia, or thrombocytopenia, or in patients on heparin therapy. Patients who are receiving low-dose heparin to prevent deep vein thrombosis should be evaluated as to the more important indication, that for prevention of deep vein thrombosis or that for epidural anesthesia. Should epidural anesthesia prove to be a greater indication, heparin therapy should be stopped 12 hours before surgery, and a partial thromboplastin time within the normal range should be obtained before starting the epidural placement. One important consideration is that...

Transfusion Reactions

In addition to the immediate or delayed haemolytic transfusion reactions referred to above, there are other types of reaction which may interfere with completion of transfusion of blood or blood components. Non-haemolytic febrile reactions, caused by recipient HLA antibodies to donor white cells, occur in 1-2 of red cell or platelet transfusions. Fever and rigors usually occur 30-60 min after the start of the transfusion. Most reactions are managed by slowing or stopping the transfusion and giving paracetamol. As platelets also express HLA antigens, there is often a failure of the platelet count to increase unless HLA-compatible platelets are used. With the introduction of universal leucode-pletion, these problems should become less prevalent.

Class 1 antiarrhythmics Class la

Quinidine is an isomer of quinine formerly used in the treatment of atrial and supraventricular tachycardias. It has antimuscarinic and a-blocking properties, the latter causing vasodilatation and decreased myocardial contractility severe hypotension may occur after i.v. administration. It may cause conduction defects or accelerate AV node conduction, accelerating ventricular rate and leading to ventricular arrhythmias. Visual and auditory disturbances with vertigo and gastrointestinal symptoms are signs of toxicity. Idiosyncratic reactions (rashes, thrombocytopenia and agranulocytosis) may also occur. Quinidine enhances digoxin toxicity by increasing plasma concentrations. It has an additive effect with other cardiodepressant drugs (e.g. disopyramide, P-blockers and calcium channel blockers) and potentiates the effects of non-depolarizing neuromuscular blockers.


Haemoglobin Men Women 10-12 years 1 year 3 months Full-term Red blood cell count (RBC) Men Women White blood cell count (WBC) Neutrophils Lymphocytes Monocytes Eosinophils Basophils Platelet count Reticulocyte count Sedimentation rate Men Women Plasma viscosity INR (international normalized ratio warfarin therapy value) Therapeutic range for Atrial fibrillation, deep venous thrombosis, pulmonary embolism, tissue heart valves Mechanical heart valve KCCT (also known as PTTK, APTT) Heparin therapy value If pregnant Platelet count Prothrombin time Thrombin time Platelet count Is platelet count decreased (< 100 x 109 L ) Peripheral destruction Immune-mediated DIC

Patient Encounter 1 Part 3 DIC Creating a Care Plan

Treatment with platelet concentrates and plasma is indicated in patients who are bleeding or who require an invasive procedure. In a bleeding patient, the platelet count should be maintained above 50 x 10 mm (50 x 10 L), and platelet concentrates should be given at a dose of 1 unit 10 kg of body weight. For patients who are not bleeding, a lower threshold of less than 10 to 20 x 103 mm3 or less than 10 to 20 x 109 L

Patient Care and Monitoring Urologic Complications

Monitor the patient for resolution of hematuria after each successive therapeutic intervention. Frequency of monitoring is based on the severity of hemorrhaging. Monitor urinary output and serum chemistries (including sodium, potassium, chloride, blood urea nitrogen, and serum creatinine) daily for renal dysfunction. Check the CBC at least daily to monitor hemoglobin and platelet count.

Anovulatory bleeding in adolescents

Anovulatory cycles are not unusual in the perimenarchal reproductive years. Ovulation typically is established a year or more following menarche. When anovulatory bleeding occurs in this population, it may be excessive. If the bleeding is excessive, the patient should be evaluated for blood dyscrasias. The prevalence of blood dys-crasias, including von Willebrand's disease and prothrombin deficiency, and the prevalence of idiopathic thrombocytopenia purpura in this population ranges from 5 to 20 .5

Preoperative Preparation Laboratory and Radiologic Tests

All patients should undergo routine laboratory testing including a complete blood count, platelet count, serum electrolytes, coagulation profile, urinalysis, and a type and screen. Any coagulopathy or urinary infection should be treated prior to proceeding with surgery. An electrocardiogram and chest radiograph should be obtained if indicated. All necessary radiologic tests (i.e., sonogram, computed tomography, and magnetic resonance imaging) should be made available for reference during the operation.

Access Emergency Medicines

Establishing the diagnosis of primary HIV infection is very important from a public health perspective. Patients are highly infectious during acute HIV secondary to an enormous viral load in both blood and genital secretions. Such patients may be unaware that they are infected and therefore may put others at risk. Clinical illness accompanies primary HIV infection in approximately two-thirds of patients. The usual time from HIV exposure to the development of symptoms is approximately 10 to 20 days, with average symptom duration of 1.5 to 2 weeks. The most common symptoms following seroconversion include fever, swollen lymph nodes, sore throat, myalgias arthralgias, diarrhea, nausea vomiting, weight loss, headache, mucocutaneous lesions, and a generalized maculopapular rash located over the face, neck, and trunk. This rash is seen in over 50 of persons with symptomatic primary HIV infection. The lesions are typically small, well-circumscribed, erythematous, nonpruritic and nontender....

Clinical Manifestations Diagnosis Treatment and Control

Laboratory findings include leukopenia, thrombocytopenia, albuminuria, and cylindruria. Serologic testing is an aid to diagnosis, but as is the case with many virus diseases, virus isolation and identification are recommended. Convalescence lasts several weeks after severe illness, and recovery is then usually complete. There are no proven specific antiviral agents but there are recent reports of successful treatment with immune plasma. When it has been given before the eighth day of illness, marked reduction in mortality has been observed. Rodent control would appear to be an obvious prevention measure, but it is not practical, given the vast areas where the virus is endemic. Much attention has been given to development of a vaccine, and at present a live attenuated vaccine shows promise of becoming useful in preventing disease in human beings. Another vaccine possibility being explored utilizes the avirulent Tacaribe virus to induce immunity against Junin.

Management of Acute Stroke

Patients suspected of having suffered an acute stroke should be stabilized in accordance with usual emergency management, which focuses initially on basic cardiopulmonary resuscitation (CPR) and support. All patients should have a thorough but timely physical examination, looking especially for head and neck trauma and cardiovascular abnormalities, followed by neurologic evaluation, including assessment of mental status, cranial nerve function, cerebellar function, and motor and sensory function, using the NIH Stroke Scale. Initial laboratory studies should generally include determination of a complete blood count (CBC) with differential and platelet count, prothrombin time and partial throm-boplastin time (PT PTT), electrolyte, blood urea nitrogen (BUN), creatinine, and glucose levels, oxygen saturation by pulse oximetry, and a metabolic panel. Depending on the clinical history, some patients should have studies for possible altered coagulation or connective tissue diseases. A CT...

Clinical Features and Associated Findings

In infants who have clinical evidence of the congenital rubella syndrome at birth, serum IgM antibody to rubella virus and viral cultures should be obtained. Other laboratory abnormalities supporting the diagnosis of congenital rubella syndrome include hyperbilirubinemia, thrombocytopenia, elevated serum transaminase levels, and long bone radiographs demonstrating metaphyseal lucencies. Neuro- imaging studies reveal intracranial calcifications, delayed myelination, or ventriculitis. y Several different methods have been used to make an intrauterine diagnosis of rubella infection including isolation of the rubella virus in the amniotic fluid obtained by amniocentesis, cordocentesis, use of the polymerase chain reaction method on extracts from chorionic villi and placenta, and ultrastructural examination of amniotic fluid cells using transmission and scanning electron microscopy. y Examination of the CSF in progressive rubella panencephalitis demonstrates a mild lymphocytic pleocytosis...

Principles of Antiepileptic Drug Treatment

Skin eruptions represent the most commonly encountered idiosyncratic reaction associated with AEDs. Generally appearing within the first 3 months of treatment, rashes are usual benign, and they resolve with dosage reduction or discontinuation. Severe reactions including Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal neurolysis occur rarely. Antiepileptic drugs can produce megaloblastic anemia, leukopenia, thrombocytopenia, aplastic anemia, asymptomatic elevations of hepatic transaminases, and life-threatening hepatotoxicity. Chronic idiosyncratic reactions include disorders of connective tissue and nervous system, endocrinopathies, and autoimmune disease.

Coronary Artery Bypass Graft Surgery

Stroke as a complication of CABG procedures occurs in 0.9 to 5.9 percent of cases. y Most territorial infarcts result from macroemboli from diseased valves, left ventricular thrombus, or atheromatous emboli from a rigid ascending aorta. Stroke occurs more frequently with valvular heart surgery than with coronary artery bypass grafting operations. A permanent neurological disability after valve replacement occurs in 5 to 10 percent of patients. In contrast, the risk of a severe disability complicating CABG surgery is less than 2 to 5 percent. y , y The difference is due to the greater risk of cardiac macroemboli with operations that require opening of the heart chambers. Removal or repair of diseased, calcified mitral or aortic valves is associated with the dispersion of tissue and surgical debris in the cardiac chambers. Extracranial carotid artery disease is often suggested as an important cause of stroke during CABG surgery. This theory proposes that severe carotid occlusive...

Platelet Function Disorders

Inherited disorders of platelet function are uncommon, although Glanzmann thrombasthenia may be seen most often. This congenital disorder has identified mutations in the GP-IIb IIIa complex. ADP-induced platelet aggregation is abnormal, as is platelet contribution to clot retraction. Abnormalities involving impaired granular release or relative absence of granules characterize Bernard-Soulier and Wiskott-Aldrich syndromes these rare disorders are also associated with thrombocytopenia. Von Willebrand's disease is an example of impaired platelet adhesion and aggregation caused by the deficiency of the von Willebrand factor, which significantly affects platelet function.


Assessment of both the degree of loss and the response to volume replacement require clinical skills, invasive hemodynamic monitoring and the early involvement of senior clinicians. There is no one correct fluid to use. It is usual to use a combination of crystalloids or colloids and blood products to maintain a hemoglobin concentration of near 10 g dl during the actively bleeding period (7-9 g dl is probably safe once the active bleeding has been stopped). Coagulo-pathies and thrombocytopenia also need to be corrected with appropriate transfusion products and with active involvement of the hematolo-gists. There may be a place for limited volume expansion before the bleeding has been stopped surgically to reduce the volume lost, but this must not be at the cost of demonstrable organ ischemia.

Coagulation Studies

With fat malabsorption syndromes, recent broad-spectrum antibiotic use, and premature infants. In addition, the use of warfarin, many drugs and herbs, severe liver disease, alcoholism, deficiencies of clotting factors, and circulating anticoagulants can prolong the PT. The PT is not affected by platelet disorders or platelet count. The target INR varies with specific indications. In general, an INR goal of 2.5 (range, 2.0-3.0) is generally accepted for the treatment of venous thromboembolic disease and atrial fibrillation, and 3.0 (range, 2.5-3.5) for patients at risk for arterial thromboembolism, including those with mechanical heart valves.


Carbamazepine frequently causes lethargy, sedation, nausea, tremor, ataxia, and visual disturbances during the acute treatment phase (Zajecka, 1993). Some patients can develop mild leukopenia or thrombocytopenia during this phase and usually do not progress. Carbamazepine has been reported to cause a severe form of aplastic anemia or agranulocytosis that is estimated to occur with an incidence of about 2 to 5 100,000. This is 11 times more likely than in the general population. While more than 80 percent of these reactions occur during the first 3 months of therapy, some cases have been reported as late as 5 years following initiation of therapy treatment. If white blood cell count drops below 3000 cells mm3, the medication should be discontinued. renal side effects associated with carbamazepine, patients should have had a recent physical examination, complete blood count (CBC) with platelet count, liver function, thyroid function, and renal indices prior to initiation of treatment....


The disorder is typically suspected in the presence of hypertension and proteinuria in the pregnant woman without history of preexisting chronic hypertension. Edema is no longer considered a reliable clinical sign and is often seen after the 20th week of gestation without signs of a hypertensive disorder. Historically, mild preeclampsia was diagnosed with a systolic BP rise of 30 mm Hg or diastolic BP rise of 15 mm Hg. Consensus statements now describe mild preeclamp-sia as an absolute reading of 140 90 mm Hg or greater in a pregnant woman with proteinuria greater than 0.3 g in a 24-hour urine collection. Again, nondependent edema is no longer considered a diagnostic criterion. Severe preeclamp-sia consists of a systolic BP greater than 160 mm Hg or diastolic BP greater than 110 mm Hg, complicated by significant proteinuria (> 5.0 g day) and evidence of end-organ damage. Signs and symptoms indicating severe preeclampsia include headache, visual disturbances, confusion, right upper...

HELLP Syndrome

If unrecognized, preeclampsia can progress to a syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). This is another complication in seemingly stable patients. The HELLP syndrome is noted in 5 to 10 of patients with preeclamptic symptoms. Such patients often present with RUQ and epigastric pain and a peripheral blood smear consistent with a microangiopathic hemolytic anemia. There may be decrements in the platelet count and increments in the transaminase (AST, ALT) and lactic acid dehydrogenase (LDH) enzymes. This is a life-threatening emergency that requires prompt delivery of the baby.

Factor IXa

People who receive heparin annually develop heparin-induced thrombocytopenia (HIT) (Blakeman, 1999) and are therefore unable to receive the drug (Eikelboom and Hankey, 2002). Patients who require repeated anticoagulation, such has those requiring renal dialysis, require viable alternatives.

Vascular Anomalies

Lab tests standard battery of neurovascular evaluation includes CBC with differential, platelet count, ESR, PT, PTT, plasma glucose, BUN, creatinine, lipid analysis, luetic serology, urinalysis. More detailed testing for hematological abnormalities are added as indicated.


The technique of the lumbar puncture (LP), or spinal tap, was first developed by Quinke in 1891 and has likely changed little since that time. Before performing an LP to obtain CSF, a patient's coagulation profile should be checked. If the results of these studies demonstrate a thrombocytopenic (platelet count less than 20,000) or a prothrombin time or partial thromboplastin time that is elevated, these abnormalities should be corrected prior to the LP. '151 In adults, the LP is best performed with the patient in the lateral decubitus position with the head and spine parallel to the floor. This positioning is particularly important for the accurate measurement of the opening and closing pressures. After positioning the patient, certain landmarks should be palpated, beginning with the iliac crest. An imaginary line that runs between the crests will intersect approximately the L3-L4 interspace. Once this area is located, the spinal processes of L3 and L4 should be palpated and between...


Currently, approximately four low-molecular-weight heparins, one heparinoid, two hirudin derivatives, and one direct thrombin inhibitor are also available for use in DVT prophylaxis. Low-molecular-weight heparins are chemical or physical fractions of unfractionated heparin and have greater bioavailability, so their anticoagulant activity is more predictable. These drugs are at least as effective as fixed-dose unfractionated heparin and less likely to cause thrombocytopenia. Subcutaneous enoxa-parin, 40 mg a day, given for one week after neurosurgical procedures appeared to be safe and effective in that the drug reduced the risk for venographically proven DVT by 50 without causing more bleeding complications than a placebo caused.14 The drug is usually used as 30-40 mg every 12 hours. Fondaparinaux, which is a newer agent derived from the activated factor X-binding moiety of unfraction-ated heparin, was more effective than enoxa-parin after hip surgery. Enoxaparin, dalteparin, and...


Transfusion support should be given to help control bleeding until the underlying cause has been dealt with and to maintain an adequate platelet count and coagulation factor levels. Platelet count If the platelet count is less than 50 x 109 L and the patient is bleeding,


Surprisingly, this condition does not respond to direct digital pressure over the ala-nasi (Hippocratic method). The management of a severe epistaxis relies on resuscitation of the patient followed by attempts to identify the source of the bleeding. The nose is examined using a headlight, nasal speculum and suction. It is often difficult to identify the bleeding point because of its posterior position. If the source cannot be found, otolaryngologists use endoscopes to examine the posterior nasal cavity and identify the bleeding vessel, which can then be cauterised under direct endoscopic vision. In the absence of specialised equipment, posterior epistaxis is usually managed by some form of tamponade, using either specially designed balloon catheters or nasal packing. Admission to hospital is required and a search for aetiological factors should be undertaken (aspirin use, alcohol excess, thrombocytopenia). Unlike childhood epistaxis, which is recurrent, adult epistaxis tends to be...

Liver Disease

Preoperative assessment should be directed towards detection of jaundice, ascites, oedema and signs of hepatic failure (encephalopathy with flapping tremor). Routine preoperative investigations should include a coagulation screen, measurement of haemoglobin concentration, white cell and platelet counts, and concentrations of serum bilirubin, alkaline phosphatase, transaminases, urea, electrolytes, proteins (including albumin) and blood sugar. Blood should also be taken to screen for viral hepatitis. Appropriate measures must be taken to protect theatre staff from possible contamination. Bleeding problems. Production of clotting factors II, VII, IX and X is reduced as a result of decreased vitamin K absorption. Production of factor V and fibrinogen is also reduced. Thrombocytopenia occurs if portal hypertension is present. Vitamin K should be administered preoperatively and fresh frozen plasma given to provide clotting factors during surgery, with regular checks made on coagulation....

Wilsons Disease

Because good recovery of hepatic and neurological function is possible in most patients, treatment must be instituted quickly. Ihe goal of therapy is to reduce copper intake by means of a low-copper diet and increase copper excretion. D-Penicillamine is the chelating agent most often used its side effects are potentially serious but preventable. Ihese include nephrotic syndrome, fever, thrombocytopenia, dermatitis, vitamin B 6 deficiency, seizures, and zinc deficiency, which causes impairment of taste and smell. Pyridoxine should be administered along with penicillamine. Some investigators suggest using tetrathiomolybdate, a drug that both blocks copper absorption and binds to bloodborne copper, as an initial therapy. In addition, zinc acetate may be used as a maintenance therapy because of its low potential for serious side effects other than gastrointestinal effects. Dietary education about foods containing high levels of copper should be undertaken, and specific...


The pathogenesis of the diseases caused by ehrlichiae are not well understood at this time. It is clear, however, that the ehrlichiae damage and lyse host phagocytic cells once they have attached to these cells resulting in leukopenia and thrombocytopenia. 106 Patients with human granulocytic ehrlichiosis present with a febrile illness associated with myalgia, headache, malaise and occasionally nausea, vomiting, or a cough. The clinical presentation may be helpful in distinguishing Lyme disease from human granulocytic ehrlichiosis. Nausea, vomiting, and cough are very infrequent in Lyme disease. Fatigue is more often a complaint with Lyme disease than with human granulocytic ehrlichiosis. The incubation period is approximately 7 days following a tick bite, and approximately 20 percent of patients with ehrlichiosis have a rash that consists of a maculopapular eruption or petechiae. w Despite the different causative agents of monocytic and granulocytic ehrlichioses, the clinical and...

Clinical Summary

The incubation period is usually 3 to 7 days with resolution of symptoms within 10 days. Clinical infection ranges from subclinical symptoms to a hemorrhagic state leading to shock. Most commonly, it is characterized by fever, severe myalgias, retro-orbital pain, and headache. The fever is often bimodal. A rash, seen in approximately 50 of cases, is usually maculopapular but may be mottled, flushed, or petechial. The disease can be graded from I to IV based upon the degree of thrombocytopenia, spontaneous bleeding, plasma leakage, and shock. These more severe forms constitute dengue, hemorrhagic fever, and dengue shock syndrome. There are four serotypes exposure to one serotype provides lifelong immunity. Previous infection with one serotype may predispose an individual to a more severe infection with another serotype. Thus, the hemorrhagic fever is more common in indigenous individuals than the previously unexposed traveler. The diagnosis is primarily clinical. The presence of...

Acute Intervention

Recent use of warfarin with prolonged INR Use of heparin within 48 hours with prolonged aPTT Platelet count < 100,000 cells mm3 History of intracranial hemorrhage Known arteriovenous malformation or aneurysm GI or GU bleeding in past 21 days Arterial puncture in past 7 days at noncompressible site Recent lumbar puncture


Pheochromocytoma should be considered in the differential diagnosis of any pregnant patient developing hypertension prior to the 20th week of gestation. The diagnosis of pheochromocytoma can be made by measuring urinary chatecholamines as with nonpregnant patients because these levels are unaffected by the pregnant state. Pre-eclampsia is high on the differential of hypertension during pregnancy but may be distinguished from pheochromocytoma by the presence of proteinuria, oliguria, and thrombocytopenia in the third trimester (108). Ultrasound and magnetic resonance imaging are the preferred localization studies.

Rheumatoid Arthritis

Clinical Features and Associated Disorders. The onset of RA is typically insidious, with prodromal malaise, fatigue, and generalized weakness. Characteristic symmetrical polyarthritis develops within weeks to months. Articular signs and symptoms preferentially affect the cervical spine and the metacarpophalangeal, proximal interphalangeal, wrist, elbow, knee, ankle, forefoot, and subtalar joints. Progression of joint disease leads to bony erosion and joint deformity. Extra-articular manifestations including rheumatoid nodules in subcutaneous, cutaneous, connective, and pulmonary tissues, pleuritis, interstitial fibrosis, pneumonitis, and pericardial effusions tend to occur in patients with high levels of circulating rheumatoid factor. Felty's syndrome (rheumatoid arthritis, splenomegaly, neutropenia, anemia, and thrombocytopenia) is seen in some patients with long-standing disease.

Clinical Cases

In 1999, a single report appeared describing a seriously ill Jehovah's Witness woman with severe pre-eclampsia complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) who died in Holland, after having received cell-salvaged blood18. It has been quoted as a 'death due to obstetric cell sal-vage'19. It should be noted, however, that a


Infant to one who has the signs and symptoms of disseminated disease. In the most severe form of congenital CMV infection, the virus affects multiple organs, and the infant has hepatitis, splenomegaly, pneumonitis, jaundice, thrombocytopenia, chorioretinitis, hemolytic anemia, petechial or purpuric rash, seizures, spasticity, microcephaly, optic atrophy, and neuroimaging evidence of intracerebral calcifications and cerebral atrophy. '129' Management. Ganciclovir and foscarnet are the two antiviral agents that have been proved effective in the treatment of CMV retinitis. CMV polyradiculopathy, encephalitis, and ventriculoencephalitis have been treated with dosing regimens that are identical to those used for CMV retinitis, although their clinical efficacy has not been established (see T ble , 4 1-6 ). Ganciclovir 5 mg kg intravenously is given twice daily during induction therapy for a minimum of 2 to 3 weeks. This is followed by maintenance therapy at a dose of 6 mg kg intravenously...


Dosing adjustments are necessary for renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. Vorinostat inhibits the activity of histone deacetylases which results in repression of gene transcription. Vorinostat is eliminated primarily by glucuronidation and hydrolysis to pharmacologically inactive metabolites, with a terminal half-life of 2 hours. Side effects include diarrhea, fatigue, nausea and anorexia, hypercholesterolemia, hypertriglyceridemia, and hyperglycemia. Despite anemia, thrombocytopenia and neut-ropenia, patients have developed pulmonary embolism and deep vein thromboses while on therapy.

Appendix D Glossary

Blood dyscrasias Any abnormality in the blood or bone marrow's cellular components such as low white or red blood cell count or low platelets Hemolytic uremic syndrome A disease characterized by microangiopathic hemolytic anemia, acute renal failure, and a low platelet count (thrombocytopenia). Heparin-induced thrombocytopenia A clinical syndrome of IgG antibody production against the heparin-platelet factor 4 complex occurring in approximately 1 to 5 of patients exposed to either heparin or low-molecular-weight heparin. Heparin-induced thrombocytopenia results in excess production of thrombin, platelet aggregation, and thrombocytopenia (due to platelet clumping), often leading to venous and arterial thrombosis, amputation of extremities, and death.

Complete Blood Count

Platelet count Platelets, cellular fragments of the bone marrow precursor-cell megakaryocytes, are essential to clot formation and have a life span of about 10 days. Clinically, a disorder in platelets is usually suspected in a patient with excessive bleeding, typically from a mucocutaneous source or after trauma. Clinical evidence of bleeding does not occur until the platelet count drops below 50 to 70 x 103 L. Platelet counts of less than 10 to 20 x 103 L are associated with major spontaneous bleeding. Thrombocytopenia may be caused by disorders of production, distribution, or destruction (Table 15-15). In evaluating thrombocytopenia, first examine the peripheral smear for platelet clumping, or repeat the test using sodium citrate as the anticoagulant. Thrombocytosis, or an increased platelet count, may be caused by a reactive process or a myeloprolif-erative disorder. Reactive processes do not usually produce platelet counts greater than 1000 x 103 L. Common causes of...

Behcets Disease

Since there is no definite test to confirm the diagnosis of BD, the constellation of symptoms and signs over time allows the diagnosis to be made. A thorough history, physical examination, and review of previous symptoms are required. ESR is likely to be elevated if there is large-vessel vasculitis but may be normal if the only evidence of disease is uveitis. Fibrin split products and platelet count may be elevated. aPL are present in 15 to 35 percent of patients. W These changes are felt to be secondary effects of the inflammatory process.

Gell and Coombs

Type II reactions are produced by IgG (or IgM) antibody. The drug or hapten that elicited the antibody response binds to target cells. When antibody binds the drug, complement activation destroys the cell. Blood dyscrasias like thrombocytopenia or hemolytic anemia are the most common examples of type II reactions.

Antitumor Efficacy

The dosage regimen of topotecan approved for clinical use is 1.5 mg m2 day given as a 30-min i.v. infusion daily for 5 days every 3 weeks. Dose-related, reversible, and noncumulative myelosuppression is the most important side effect of topotecan (229). Neutropenia - the nadir is usually approximately 9 days after the start of the treatment and the median duration is approximately 7-10 days - occurred more frequently and is often more severe than thrombocytopenia. Also, neutropenia was more severe in heavily pretreated patients compared with minimally pretreated patients (229). Besides myelosuppression, stomatitis (24-28 of patients) and late-onset diarrhea (40 ) were noted at higher doses (65,229). Other nonhematological toxicities reported included alopecia (76-82 of patients), nausea (75-78 ), vomiting (53-64 ), fatigue (30-41 ), and asthenia (21-22 ) (229).


Thrombocytosis can be a primary marrow-related disorder or secondary reactive to a surgical or medical condition and is defined as a platelet count greater than 500,000 uL. Primary marrow related thrombocytosis may occur in the face of a chronic myeloproliferative or myelodysplastic disorder such as polycythemia vera (PV), primary myelofibrosis (MF), chronic myelogenous leukemia (CML) and essential thrombocythemia (ET). ET can be diagnosed by eliminating secondary causes and the other myeloproliferative disorders. (See earlier section Myeloproliferative Disorders). Secondary or reactive thrombocytosis can occur in the setting of infection, post surgical conditions with and without infection, cancer, postsplenectomy, acute blood loss or iron deficiency. Other situations, such as celiac disease, amyloidosis, rheumatoid arthritis, or rebound after alcohol- or drug-induced thrombocytopenia, can lead to thrombocytosis as well. Symptoms are more likely to be associated with primary rather...

Heparin Pharmacology

Of platelets a dependence on antithrombin levels nonspecific binding to plasma protein an inability to inhibit clot bound thrombin and direct binding to platelet factor-4 contributing to heparin induced thrombocytopenia in 1 to 3 of treated patients. Platelet activation by heparin is evidenced by an increase in the expression of platelet surface adhesion molecules.12 Nonspecific binding to plasma proteins secreted by platelets and endothelial cells in the setting of inflammation, and thrombosis may contribute to reduced bioavailability.13 The heparin-antithrombin complex results in a large molecular structure that has limited capacity to access thrombin and FXa bound within thrombus.14 The LMWHs are produced by chemical or enzymatic depolymerization of unfractionated heparin, resulting in heparin fragments with a mean molecular weight that is approximately 30 of most unfractionated heparin preparations. However, the molecular size of the heparin molecules still varies, and...


The second most important step is to send an urgent blood sample to the laboratory for baseline readings of full blood count, including hemoglobin, hematocrit and platelet count, plus clotting tests, including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen levels as a baseline. A biochemical profile and blood gas analysis are also useful, especially to measure the level of acidosis and base deficit. Because of the often rapid changes occurring, it is essential throughout the episode Platelets should be transfused only to prevent or correct bleeding associated with a decrease in platelet count or abnormality of platelet function as they are difficult to store and in short supply16. Anticipate platelet count < 50 x 109 l Target platelet count -


Neuraxial anesthesia is contraindicated in the presence of a coagulopathy. Spinal hematoma may result in permanent neurologic damage if not diagnosed and decompressed within 6 to 12 hours after onset of symptoms.1323 Unfortunately, it is often difficult to assess whether patients with abnormal laboratory coagulation parameters have a clinical coagulopathy. In general, an international normalized ratio greater than 1.41113 or a prolonged aPTT are considered contraindications to neuraxial anesthesia.1153 Platelet count and function are discussed earlier under the heading Preeclampsia-Eclampsia.

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