Thrombocytopenia: an overview

Immune thrombocytopenia is an acquired isolated thrombocytopenia from antiplatelet autoantibody-mediated destruction plus impaired marrow production, presenting with mucocutaneous bleeding and no splenomegaly. It is a diagnosis of exclusion made by a normal smear and normal other cell lines, and treatment is driven by bleeding risk, starting with glucocorticoids with or without IVIG or anti-D.

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency that lets ultralarge von Willebrand factor multimers drive platelet microthrombi; the key dyad of microangiopathic hemolytic anemia plus thrombocytopenia without another cause mandates the PLASMIC score, an ADAMTS13 activity and inhibitor level, and emergent plasma exchange started before results return.

Heparin-induced thrombocytopenia is an immune, prothrombotic drug reaction in which IgG antibodies against platelet factor 4-heparin complexes activate platelets, causing venous and arterial thrombosis alongside a paradoxical falling platelet count. The danger is clotting, not bleeding, so management is to stop all heparin immediately and start a non-heparin anticoagulant while avoiding platelet transfusion and premature warfarin.

Disseminated intravascular coagulation is a secondary, systemic activation of coagulation and fibrinolysis, most often from sepsis, that simultaneously consumes platelets and clotting factors, causing microvascular thrombosis and bleeding. Diagnosis rests on a laboratory constellation, thrombocytopenia, prolonged PT and aPTT, low fibrinogen, and elevated D-dimer, in a predisposing clinical setting, and management centers on treating the underlying trigger while replacing blood components only for active or high-risk bleeding.

Platelet disorders span a quantitative axis (thrombocytopenia from decreased production, increased destruction, or sequestration) and a qualitative axis (normal-count platelets that fail to adhere or aggregate), plus reactive or clonal thrombocytosis, and all present with mucocutaneous bleeding rather than deep hematomas. Diagnosis starts with a platelet count and smear to exclude pseudothrombocytopenia, adds platelet function testing when the count is normal but bleeding is mucocutaneous, and management is cause-directed.

Hemolytic uremic syndrome is a thrombotic microangiopathy defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, most often triggered in children by Shiga toxin-producing Escherichia coli O157:H7 after bloody diarrhea. Diagnosis rests on schistocytes with a negative Coombs test plus a normal ADAMTS13 level to exclude TTP, and typical STEC-HUS is managed supportively while antibiotics and antimotility agents are avoided, whereas complement-mediated atypical HUS requires eculizumab.

Aplastic anemia is an acquired or inherited hematopoietic stem cell disorder that produces pancytopenia with a hypocellular, fatty bone marrow and no dysplasia, blasts, or fibrosis. Diagnosis rests on marrow biopsy showing less than 25% cellularity with severity graded by the Camitta criteria, and treatment is allogeneic stem cell transplantation for young fit patients with a matched donor or antithymocyte globulin plus cyclosporine and eltrombopag for everyone else.

Myelodysplastic syndromes are clonal stem cell disorders producing ineffective hematopoiesis: a dysplastic, usually hypercellular bone marrow with peripheral cytopenias and a variable risk of transformation to acute myeloid leukemia. Diagnosis requires bone marrow biopsy showing dysplasia after excluding reversible mimics, risk is stratified with the IPSS-R, and treatment ranges from supportive transfusions and lenalidomide in lower-risk disease to hypomethylating agents and allogeneic transplant, the only cure, in higher-risk disease.