(See also Overview of Platelet Disorders Overview of Platelet Disorders Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes,... read more 
.)
Acute respiratory distress syndrome
Patients with acute respiratory distress syndrome Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is severe arterial hypoxemia that is refractory to supplemental oxygen. It is caused by intrapulmonary shunting of blood resulting from airspace filling or... read more 
may develop nonimmunologic thrombocytopenia, possibly secondary to deposition of platelets in the pulmonary capillary bed.
Blood transfusions
Posttransfusion purpura involves immunologic platelet destruction indistinguishable from immune thrombocytopenia Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more 
(ITP), except for a history of a blood transfusion within the preceding 7 to 10 days. The patient, usually a woman, lacks a platelet antigen (PLA-1) present in most people. Transfusion with PLA-1–positive platelets stimulates formation of anti–PLA-1 antibodies, which (by an unknown mechanism) can react with the patient’s PLA-1–negative platelets. Severe thrombocytopenia results, taking 2 to 6 weeks to subside. Treatment with IV immune globulin (IVIG) is usually successful.
Connective tissue and lymphoproliferative disorders
Connective tissue (eg, systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more 
, antiphospholipid antibody syndrome Antiphospholipid Antibody Syndrome (APS) Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is... read more ) or lymphoproliferative disorders (eg, chronic lymphocytic leukemia [CLL or LGL leukemia] Chronic Lymphocytic Leukemia (CLL) Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of phenotypically mature malignant B lymphocytes. Primary sites of disease include peripheral blood, bone marrow... read more ) can cause secondary ITP. Corticosteroids and the usual treatments for immune thrombocytopenia Treatment Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more are often effective; treating the underlying disorder does not always lengthen remission and may not be necessary.
Drug-induced immunologic destruction
Commonly used drugs that occasionally induce thrombocytopenia include
Heparin
Quinine
Trimethoprim/sulfamethoxazole
Glycoprotein IIb/IIIa inhibitors (eg, abciximab, eptifibatide, tirofiban)
Hydrochlorothiazide
Carbamazepine
Chlorpropamide
Ranitidine
Rifampin
Vancomycin
Drug-induced thrombocytopenia occurs typically when a drug bound to the platelet creates a new and “foreign” antigen, causing an immune reaction. This disorder is indistinguishable from ITP except for the history of drug ingestion. When the drug is stopped, the platelet count typically begins to increase within 1 to 2 days and recovers to normal within 7 days. (A table of drugs reported to cause thrombocytopenia, together with analysis of the evidence for a causal relation of the drug to thrombocytopenia, is available at Platelets on the Web.)
Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia (HIT) occurs in up to 1% of patients receiving unfractionated heparin. Heparin-induced thrombocytopenia may occur even when very-low-dose heparin (eg, used in flushes to keep IV or arterial lines open) is used. The mechanism is usually immunologic. Bleeding rarely occurs, but more commonly platelets clump excessively, causing vessel obstruction, leading to paradoxical arterial and venous thromboses, which may be life threatening (eg, thromboembolic occlusion of limb arteries, stroke Overview of Stroke Strokes are a heterogeneous group of disorders involving sudden, focal interruption of cerebral blood flow that causes neurologic deficit. Strokes can be Ischemic (80%), typically resulting... read more 
, acute myocardial infarction Acute Myocardial Infarction (MI) Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and diaphoresis.... read more 
).
Heparin should be stopped immediately in any patient who becomes thrombocytopenic and develops a new thrombosis or whose platelet count decreases by more than 50% while tests are done to detect antibodies to heparin bound to platelet factor 4. Anticoagulation with a nonheparin anticoagulant (eg, argatroban, bivalirudin, fondaparinux) should be substituted at least until platelet recovery.
Low-molecular-weight heparin (LMWH) is less immunogenic than unfractionated heparin but cannot be used to anticoagulate patients with heparin-induced thrombocytopenia because most HIT antibodies cross-react with LMWH. Fondaparinux is an acceptable alternative in many patients but given its long 17-hour half-life, is not appropriate in those patients who may soon need a procedure or have a high bleeding risk. Warfarin should not be substituted for heparin in patients with heparin-induced thrombocytopenia and, if long-term anticoagulation is required, should be started only after the platelet count has recovered.
Infections
HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more 
may cause immunologic thrombocytopenia indistinguishable from immune thrombocytopenia Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more except for the association with HIV. The platelet count may increase when glucocorticoids are given. However, glucocorticoids are often withheld unless the platelet count falls to < 20,000/mcL because these drugs may further depress immune function. The platelet count also usually increases after treatment with antiviral drugs.
Hepatitis C Hepatitis C, Acute Hepatitis C is caused by an RNA virus that is often parenterally transmitted. It sometimes causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice but may be asymptomatic... read more infection is commonly associated with thrombocytopenia. Active infection can create a thrombocytopenia that is indistinguishable from immune thrombocytopenia with platelets < 10,000/mcL. Milder degrees of thrombocytopenia (platelet count 40,000 to 70,000/mcL) may be due to liver damage that reduced production of thrombopoietin, the hematopoietic growth factor that regulates megakaryocyte growth and platelet production. Hepatitis C-induced thrombocytopenia responds to the same treatments as does immune thrombocytopenia Treatment Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more .
Other infections, such as systemic viral infections (eg, Epstein-Barr virus Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more 
, cytomegalovirus Cytomegalovirus (CMV) Infection Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. A syndrome of infectious mononucleosis that lacks severe pharyngitis is common. Severe... read more ), rickettsial infections (eg, Rocky Mountain spotted fever Rocky Mountain Spotted Fever (RMSF) Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii and transmitted by ixodid ticks. Symptoms are high fever, severe headache, and rash. (See also Overview of Rickettsial... read more 
), and bacterial sepsis, are often associated with thrombocytopenia.
Pregnancy
Thrombocytopenia, typically asymptomatic, occurs late in gestation in about 5% of normal pregnancies (gestational thrombocytopenia); it is usually mild (platelet counts < 70,000/mcL are rare), requires no treatment, and resolves after delivery. However, severe thrombocytopenia may develop in pregnant women with preeclampsia Preeclampsia and Eclampsia Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more and the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets); such women typically require immediate delivery, and platelet transfusion is considered if platelet count is < 20,000/mcL (or < 50,000/mcL if delivery is to be cesarean).
Sepsis
Sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more often causes nonimmunologic thrombocytopenia that parallels the severity of the infection. The thrombocytopenia has multiple causes:
Formation of immune complexes that can associate with platelets
Activation of complement
Deposition of platelets on damaged endothelial surfaces
Removal of the platelet surface glycoproteins resulting in increased platelet clearance by the Ashwell-Morell receptor in the liver
Platelet apoptosis
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
immune globulin |
Gammagard S/D |
heparin |
No US brand name |
quinine |
QUALAQUIN |
trimethoprim/sulfamethoxazole |
BACTRIM, SEPTRA |
abciximab |
REOPRO |
eptifibatide |
INTEGRILIN |
tirofiban |
AGGRASTAT |
hydrochlorothiazide |
MICROZIDE |
carbamazepine |
TEGRETOL |
chlorpropamide |
DIABINESE |
ranitidine |
No US brand name |
rifampin |
RIFADIN, RIMACTANE |
vancomycin |
VANCOCIN |
argatroban |
No US brand name |
bivalirudin |
ANGIOMAX |
fondaparinux |
ARIXTRA |
warfarin |
COUMADIN |
