Thrombocytopenia and Platelets

Chapter 55 Thrombocytopenia and Platelets



Chad T. Wilson, MD, MPH , Hasan B. Alam, MD, FACS




1 What are two principal functions of platelets in effecting hemostasis?


Platelets function to effect hemostasis by the following:



image Formation of an initial platelet plug


image Degranulation and secretion of proteins and catalysts for the clotting cascade


The initial platelet plug is due to loose aggregation of platelets in an area of injury and requires the presence of von Willebrand factor. Heparin does not affect this primary hemostasis, which explains why hemostasis can still occur in heparinized patients.



2 What is the most common congenital platelet deficiency?


von Willebrand disease. The absence of von Willebrand factor disrupts the formation of platelet aggregates (see question 1).



3 Define thrombocytopenia


No single value for platelet count universally defines thrombocytopenia; however, conventionally, platelet count of less than 100,000/mm3 is considered to constitute thrombocytopenia.



4 What are the basic mechanisms of thrombocytopenia?


Thrombocytopenia can be caused by decreased platelet production (marrow failure or replacement by cancerous cells or fibrosis), disordered platelet distribution or sequestration (hypersplenism), or increased platelet destruction (antibody mediated, prosthetic valves, extracorporeal bypass, disseminated intravascular coagulation [DIC]). These mechanisms can occur in isolation or in combination.



5 How prevalent is thrombocytopenia in critically ill patients, and what are the most common causes of thrombocytopenia in the intensive care unit (ICU)?


Thrombocytopenia has a prevalence of 30% to 50% of patients in the ICU. Some of the most common causes of thrombocytopenia in the ICU are recent surgery and hemorrhage, blood transfusions, drug-induced thrombocytopenia, intravascular catheters or aortic balloon pumps and vascular grafts, sepsis, renal replacement therapy, DIC, and myelodysplastic and metastatic disease. Most patients who have thrombocytopenia in the ICU have multifactorial causes or idiopathic thrombocytopenia.



6 What are the most common agents used in the ICU that cause drug-induced thrombocytopenia?




image Antibiotics: for example, linezolid, vancomycin, β-lactams


image Glycoprotein (GP) IIb/IIIa inhibitors: abciximab, eptifibatide, lotrifiban


image Histamine 2 (H2) blockers: cimetidine, famotidine, ranitidine


image Antiseizure: valproic acid, phenytoin


image Heparin: unfractionated heparin and low-molecular-weight heparin



7 What is heparin-induced thrombocytopenia (HIT)?


HIT is a life- and limb-threatening prothrombotic complication of heparin administration (risk of 0.6% with unfractionated heparin and 0.3% with low-molecular-weight heparin in a recent large multicenter trial of ICU patients). It results from an immune response triggered by the interaction of heparin with a specific platelet protein, platelet factor 4 (PF4). Certain patient populations are at higher risk than others for development of HIT, with patients after cardiac surgery having a risk of HIT that can be greater than 2%. HIT with thrombotic complication has a mortality rate of 20%, with approximately 20% to 30% having permanent disability (i.e., amputations, stroke).



8 When should a patient have a work-up for HIT?


The diagnosis must be considered in any patient in whom thrombocytopenia develops, who has an unexplained fall in platelet count of 50%, or who has thrombotic complication 5 to 10 days (may be as late as 20 days) after heparin exposure.



9 How is HIT diagnosed?


Almost all the patients with HIT have circulating antibodies to complexes between PF4 and heparin. However, in most of the patients who have circulating antibodies, HIT does not develop clinically. Therefore it is currently not indicated to screen patients without symptoms for these antibodies. Two different types of assays are available:



image The functional assays measure heparin-dependent platelet activation by PF4-heparin antibody in vitro. One of the functional assays, 14C-serotonin release assay (SRA), is considered the gold standard in diagnosis with a positive predictive value of almost 100% (but a negative predictive value of approximately 20%).


image Immunoassays (such as enzyme-linked immunosorbent assay [ELISA]) measure the levels of antibodies in circulation (sensitivity 93%-97%, positive predictive value 93%-100%, specificity 86%-100%, and negative predictive value 88%-95%). ELISA is easy and rapid to obtain, but only 25% of the ELISA-positive specimens are SRA positive.



10 Is repeating HIT testing useful?


Testing should be repeated for negative but borderline ELISA results. The chances of a negative test turning positive 3 days later depends on the titer levels. Approximately 45% of high-titer negative (almost positive) may turn positive, whereas approximately 15% and 5% of the medium- and low-titer results respectively are likely to turn positive.

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Jul 7, 2016 | Posted by in CRITICAL CARE | Comments Off on Thrombocytopenia and Platelets

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