Platelet destruction can develop because of immunologic causes (viral infection, medications, systemic rheumatic or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis, vascular malformations, acute respiratory distress syndrome). Manifestations are petechiae, purpura, and mucosal bleeding. Laboratory findings depend on the cause. The history may be the only suggestion of the diagnosis. Treatment is correction of the underlying disorder.
(See also Overview of Platelet Disorders.)
Acute respiratory distress syndrome
Patients with acute respiratory distress syndrome 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 (ITP), except for a history of a blood transfusion within the preceding 7 to 10 days. The patient, usually a female, 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.
Systemic rheumatic and lymphoproliferative disorders
Systemic rheumatic disorders (eg, systemic lupus erythematosus, antiphospholipid syndrome) or lymphoproliferative disorders (eg, chronic lymphocytic leukemia [CLL]) can cause secondary ITP. Corticosteroids and the usual treatments for immune thrombocytopenia are often effective; treating the underlying disorder does not always lengthen remission.
Medication-induced platelet destruction
Commonly used medications that occasionally induce thrombocytopenia include
Chlorpropamide
Trimethoprim/sulfamethoxazole
Except for heparin, medication-induced thrombocytopenia occurs typically when a medication bound to the platelet or a carrier protein creates a new and “foreign” antigen, causing an immune reaction. This disorder is indistinguishable from ITP except for the history of medication use. When the medication is stopped, the platelet count typically begins to increase within 1 to 2 days and recovers to normal within 7 days.
Heparin-induced thrombocytopenia
HeparinHeparin-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, acute myocardial infarction).
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% pending results of tests done to detect antibodies to heparin bound to platelet factor 4.
Low-molecular-weight heparin (LMWH) is less immunogenic than unfractionated heparin but cannot be used to anticoagulate patients with heparinheparin in patients with heparinwarfarin should be started only after the platelet count has recovered.
Infections
HIV infection may cause immunologic thrombocytopenia indistinguishable from immune thrombocytopenia 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 (< 20 × 109/L) because glucocorticoids may further depress immune function. The platelet count also usually increases after treatment with antiviral drugs.
Hepatitis C infection is commonly associated with thrombocytopenia. Active infection can create a thrombocytopenia that is indistinguishable from immune thrombocytopenia with platelets < 10,000/mcL (< 10 × 109/L). Milder degrees of thrombocytopenia (platelet count 40,000 to 70,000/mcL [40 to 70 × 109/L]) 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.
Other infections, such as systemic viral infections (eg, Epstein-Barr virus, cytomegalovirus), rickettsial infections (eg, Rocky Mountain spotted fever), and bacterial sepsis, often accompany 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 [< 70 × 109/L] are rare), requires no treatment, and resolves after delivery. However, severe thrombocytopenia may develop in pregnant patients with preeclampsia and the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets); such patients typically require immediate delivery, and platelet transfusion is considered if platelet count is < 20,000/mcL (< 20 × 109/L), or < 50,000/mcL (< 50 × 109/L) if delivery is to be cesarean (1).
Sepsis
Sepsis often causes nonimmunologic thrombocytopenia that parallels the severity of the infection. The thrombocytopenia has multiple causes:
Activation of complement
Deposition of platelets on damaged endothelial surfaces
Formation of immune complexes that can associate with platelets
Platelet apoptosis
Removal of the platelet surface sialic acid, resulting in increased platelet clearance by the liver mediated by hepatocyte Ashwell-Morell or Kupffer cell CLEC4F receptors
Reference
1. Fogerty AE, Kuter DJ. How I Treat Thrombocytopenia in Pregnancy. Blood Published online November 22, 2023. doi:10.1182/blood.2023020726
