Where have all the platelets gone? HIT, DIC, or something else?

Abstract

Thrombocytopenia in ill children is common; accurately diagnosing the underlying etiology is challenging and essential for appropriate management. Triggers for accelerated consumption of platelets are numerous; common downstream mechanisms of clearance include platelet trapping in microvascular thrombi, phagocytosis, and platelet activation. Thrombocytopenia with microangiopathic hemolytic anemia (MAHA) is frequently due to disseminated intravascular coagulation. Thrombotic microangiopathy (TMA) is a subgroup of MAHA. Specific TMA syndromes include thrombotic thrombocytopenic purpura, complement-mediated TMA (CM-TMA), and Shiga toxin-mediated hemolytic uremic syndrome. Isolated thrombocytopenia is characteristic of immune thrombocytopenia; however, concomitant cytopenias are frequent in critically ill patients, making the diagnosis difficult. Immune thrombocytopenia with large vessel thrombosis is a feature of heparin-induced thrombocytopenia and antiphospholipid antibody syndrome. In addition, thrombocytopenia is common with macrophage activation, which is characteristic of hemophagocytic lymphohistiocytosis. While thrombocytopenia in ill patients can be driven by hypoproliferative processes such as myelosuppression and/or bone marrow failure, this review will focus on consumptive thrombocytopenia due to immune and nonimmune causes.

Graphical abstract

Figure 1.

Clinical case 1: heparin induced thrombocytopenia (HIT). (A) Time course for platelet count (blue) with heparin exposure demonstrates characteristic pattern of HIT. The platelet factor 4 (PF4) immunoassay was strongly positive (OD  =  1.39; cutoff for positivity OD ≥0.4), and the serotonin release assay (SRA) was positive. Platelet count recovered after discontinuation of heparin and transition to a direct thrombin inhibitor, bivalirudin, and then rivaroxaban. (B) 4T score for pretest probability of HIT. The patient scored a high probability of HIT with a score of 8. DVT, deep vein thrombos; OD, optical density; PE, pulmonary embolism; UFH, unfractionated heparin.

Figure 2.

Patterns of thrombocytopenia for HIT and conditions confused for HIT. (A) Time course for drop in platelets (blue) in response to increase in HIT antibody titer (orange squares). Recovery of platelet count with discontinuation of heparin and transition to direct thrombin inhibitor. (B) Rapid onset HIT. Patient was previously treated with heparin and developed rapid onset of thrombocytopenia with heparin exposure. (C) Thrombocytopenia with extracorporeal membrane oxygenation (ECMO)—not HIT. Rapid and sustained thrombocytopenia is seen with initiation of ECMO due to platelet consumption within the circuit. (D) Thrombocytopenia after cardiopulmonary bypass (CPB)—not HIT. Platelet drop within 1-3 days after CPB, followed by recovery.

Figure 3.

Clinical case 3: thrombotic thrombocytopenic purpura (TTP). (A) Patient presented with severe and selective thrombocytopenia (blue). Platelets did not improve after intravenous immunoglobulin (IVIG) treatment for presumptive immune thrombocytopenia (ITP). Patient developed a progressive decrease in hemoglobin (orange), and markers of hemolysis consistent with a microangiopathic anemia. Platelet count normalized with plasmapheresis and steroids. INR, international normalized ratio; LDH, lactate dehydrogenase; MCV, mean corpuscular hemoglobin; WBC, white blood cells. (B) PLASMIC score was high, compatible with TTP.

Figure 4.

Clinical case 3: disseminated intravascular coagulation (DIC). (A) Patient with pneumonia develops a rapid drop in platelet count (blue) and increased white count (orange) with microangiopathic hemolytic anemia and high D dimer. Thrombotic thrombocytopenic purpura (TTP) was considered given neurologic symptoms, and plasmapheresis was initiated. The patient recovered with antibiotic treatment for pneumonia and sepsis. (B) International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score high, compatible with overt DIC.