Thrombocytopenia

Bernard Soulier syndrome

AR disorder -absent platelet glycoprotein Ib-IX-V which is a receptor for VWF -mild thrombocytopenia, giant circulating platelets, severe platelet dysfunction, and bleeding OUT OF PROPORTION to degree of thrombocytopenia

ITP Treatment

Both glucocorticoids and intravenous immune globulin (IVIG) are effective therapies, but thrombocytopenia often relapses when treatment is discontinued. -In chronic cases ITP, risks of prolonged therapy must weigh against benefits -Another second-line immunosuppressive agent, rituximab, a chimeric monoclonal antibody directed against the CD20 surface marker on B lymphocytes, will lead to doubling of the platelet count in 40% of patients. -Thrombopiesis stimulating agents like romiplostim or eltrombopag, are also effective augmenting platelet counts in patients with ITP -Rarely, patients with significant bleeding unresponsive to immunosuppressive medication require splenectomy

Heparin-Induced Thrombocytopenia

Develops in 1-2% patients receiving UFH -Incidence 2-3x lower in patients receiving LMWH -Patients undergoing open-heart surgery have a higher incidence HIT than those receiving prophylaxis -prolongs aPTT -decrease of approximately 50% in platelet count from baseline levels, 5 to 10 days after initiating heparin therapy. Perhaps 5% of patients will have delayed thrombocytopenia a mean of 14 days after heparin exposure, and those patients may have the first clinical signs of HIT noted after the heparin has been discontinued -Thrombocytopenia nadir in HIT is modest; mean platelet counts are approximately 60,000/µL (60 × 109/L), and patients typically do not bleed excessively. To the contrary, patients with HIT have a dramatic risk of thromboembolic complications

Treatment HIT

Heparin must be discontinued and an alternative rapidly acting anticoagulant must be used instead. Warfarin is not a suitable alternative agent. Direct thrombin inhibitors (eg, lepirudin or argatroban) should be administered

Diagnosis TTP-HUS

Microangiopathic hemolysis with prominent schistocytes on peripheral blood smear -↓ haptoglobin, elevated LDH, thrombocytopenia -Assay for ADAMTS13 -Malignant hypertension, disseminated intravascular coagulation, and prosthetic heart valves can be associated with microangiopathic hemolysis, although the additional presence of thrombocytopenia and fever, kidney, and neurologic findings strongly supports the diagnosis of TTP-HUS.

Immune Thrombocytopenic Purpura

Occurs when antibodies targeting platelet antigens mediate accelerated destruction. -arise in 3 distinct clinical settings: in response to drug, in a/w disease, and idiopathic -diseases affecting immune regulation, such as HIV infection, systemic lupus erythematosus, and, especially in older patients, lymphoproliferative malignancy, H pylori -commonly present with easy bruising or petechial rash. At times, asymptomatic thrombocytopenia is noted on routine blood tests., most common in patients with isolated thrombocytopenia -thrombotic microangiopathy (↓ platelets and hemolytic anemia)

Type 1 versus Type 2 HIT

Type 2 is immune mediated due to antibodies against platelet 4 receptor complexes -pro-thrombotic states

Presentation ITP

antecedent viral infection easy bruising or petechial rash -physical examination is normal, with the exception of signs of bleeding, most often petechiae (punctuate red macular lesions that do not blanch with pressure) on the skin or mucous membranes. Patients may have ecchymoses on the skin or more overt bleeding, especially in the gastrointestinal tract -Blood smear: ↓ platelets, megathrombocytes IgG autoantibodies against the platelet membrane→ ↑ platelet destruction and inhibition of megakaryocytic platelet destruction Dx: peripheral smear, CBC, testing for Hep B and C

Thrombotic Thrombocytopenia Purpura-Hemolytic Uremic Syndrome

develop consumptive thrombocytopenia and microangiopathic hemolysis from platelet thrombi that form throughout the microvasculature. - Fever, acute kidney injury, and fluctuating neurologic abnormalities are components of the syndrome, but all are seldom present during earlier phases of the illness -Patients with little to no kidney involvement and prominent neurologic symptoms fall more into the TTP category, whereas those with acute kidney injury and fewer neurologic manifestations (often seen in children with significant diarrhea) fit better with HUS -Most patients with TTP have an autoantibody that inhibits a metalloproteinase (ADAMTS13) that normally cleaves unusually large von Willebrand factor multimers into smaller fragments→ accumulation of large vWF multimers and platelet aggregation -Children develop HUS with prominent gastrointestinal symptoms from Shiga toxin-producing enteric bacteria (eg, Escherichia coli O157:H7). Ticlopidine, clopidogrel, cyclosporine, AIDS, SLE can cause TTP too

HIT panel

laboratory tests will reveal antibodies that cause heparin-induced serotonin release or platelet aggregation

Drugs related to ITP

most often linked to quinine or quinidine. -include ranitidine, trimethoprim-sulfamethoxazole, rifampin, phenytoin, and gold compounds. The glycoprotein IIb/IIIa platelet inhibitors, such as abciximab, have also been associated with an acute onset and severe thrombocytopenia.

Treatment TTP-HUS

plasma exchange transfusion, although young patients with features suggesting enteric bacterial toxins as the etiology have a much better prognosis and may be managed supportively. -Glucocorticoids are also recommended. Patients with more severe disease, especially with prominent neurologic manifestations, or those with delayed response to plasma exchange and glucocorticoids, may be treated with alternative immunosuppressive agents (eg, rituximab). Platelet transfusions in patients with untreated TTP-HUS are associated with acute kidney injury, stroke, and sudden death.

2 mechanisms thrombocytopenia

↓ platelet production or accelerated platelet destruction