Quantitative Platelet Disorders

Thrombocytopenia occurs when the platelet count falls below 150,000 per microliter of blood. The risk of bleeding becomes significant when counts drop to 50,000 per microliter, while spontaneous bleeding is common at counts below 20,000 per microliter. As a quantitative platelet disorder, thrombocytopenia lengthens bleeding time but has no impact on prothrombin time (PT) or activated partial thromboplastin time (aPTT).

Immune thrombocytopenia (ITP) is a frequent cause of thrombocytopenia and is initiated by IgG autoantibodies targeting glycoprotein 2b/3a receptors on platelets. These coated platelets are removed by splenic macrophages. Pediatric ITP commonly affects children between 2-5 years old and often follows a viral infection that triggers an abnormal autoimmune response. Symptoms such as petechiae, epistaxis, and easy bruising are typical. Pediatric ITP generally lasts 3-6 months in children and usually requires only conservative treatment.

Adult ITP follows chronic course with periodic acute flares, and can result from both infectious and autoimmune etiologies. It frequently affects young women in their 20s and 30s. Corticosteroids serve as the primary treatment for immunosuppression, and intravenous immunoglobulin (IVIG) is used in severe cases to manage acute flares. In refractory cases, a splenectomy may be performed to halt the phagocytosis of platelets by splenic macrophages, thereby increasing platelet counts.

Another form of thrombocytopenia is heparin-induced thrombocytopenia (HIT), which occurs after administration of unfractionated heparin (UFH). It is mediated by autoantibodies that bind to the platelet factor 4-heparin complex and directly to platelets via their Fc region. This antibody binding triggers platelet degranulation, leading to the release of cytokines, platelet factor 4, and ADP, which induce clot formation. The resulting platelet activation causes deep vein thrombosis (DVT) and pulmonary embolism, though arterial thrombosis occurs less frequently.

The primary cause of HIT is the phagocytosis of IgG-coated platelets , though systemic thrombosis and platelet consumption also play a role. Clinically, HIT often presents with subtle symptoms such as fever, chills, tachycardia, or dyspnea. Treatment consists of anticoagulation with direct thrombin inhibitors like bivalirudin or argatroban.

Hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are both thrombotic microangiopathies that cause diffuse platelet activation, leading to thrombocytopenia due to widespread thrombus formation and platelet consumption. These conditions increase the shear force on erythrocytes, leading to hemolysis and microangiopathic hemolytic anemia (MAHA).

In HUS, over 90% of cases are caused by infection with enterohemorrhagic E. coli (EHEC). EHEC is commonly transmitted through undercooked meat or unpasteurized dairy, and produces a Shiga-like toxin responsible for the development of HUS. This toxin induces damage to capillary endothelial cells, leading to inflammation, thrombosis, MAHA, and thrombocytopenia. The HUS triad of findings consists of thrombocytopenia, MAHA, and acute kidney injury (AKI).

Thrombotic thrombocytopenic purpura (TTP) is most commonly observed in young women and involves the development of autoantibodies against the protease ADAMTS13. A deficiency in this protease, which normally cleaves large von Willebrand factor (vWF) complexes, leads to the activation and cross-linking of platelets, resulting in intravascular thrombosis. Both the HUS triad and additional symptoms like fever and neurological manifestations are part of the TTP pentad.

Other causes of thrombocytopenia can include splenomegaly, such as in portal hypertension, and bone marrow suppression from drugs, infection, cancer, or other factors.