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Thrombocytopenia Jason Corbeill PA-C Platelet facts Chunks of cytoplasmic fragments of a megakaryocyte (in bone marrow) Surface contains receptors Cytoplasm contains secretory granules Lives 8-10 days 1/3 is sequestered in spleen (emergency pool) Platelet function 1. ACTIVATES and releases messenger molecules/effector enzymes 2. ADHERES to area of broken vessel utilizing Von Willebrand factor. 3. Recruits additional platelets (AGGREGATION) with fibrinogen binding to platelet surface receptors. 4. PROMOTES thrombin production The numbers Normal is 150-400k Below 125 or so is concerning Below 50k is very concerning and surgeries should be postponed Below 10-20k requires PLT transfusion-risk for spontaneous bleed. Refer to hematologist Signs/Symptoms of low platelets Bleeding in areas of weak structural support (mucous membranes) Bleeding in areas of dependency (ankles) Signs/Symptoms cont. Petechiae—small 2-5mm deep red – purple flat, non palpable lesions usually in dependent areas Purpura—areas of confluent petechiae— can be a few centimeters “blood blisters”—purpura in mouth Gingival bleeding menorrhagia Signs/Symptoms cont GI bleeding Easy bruising Hematuria CNS bleed 3 mechanisms causing a low platelet count : Accelerated destruction Impaired production Abnormal distribution (hypersplenism) Differential of thrombocytopenia due to accelerated destruction EDTA clumping—lab abnormality ITP-idiopathic (immune) thrombocytopenic purpura and it’s mimics. HUS-TTP DIC/sepsis Alcohol induced Hereditary HIT (heparin induced thrombocytopenia) A word about true ITP Caused by splenic destruction of PLT due to autoantibody (immune response) that views the platelet as foreign Red and white cells are normal Bone marrow is normal No splenomegaly No lymphadenopathy Peripheral smear is normal (exc low PLT) Mimics of ITP via immunologic pathway Lupus Lymphoma CLL Infections (including HIV) Sarcoidosis Solid tumors Mononucleosis Drugs—quinine, quinidine, gold, heparin, sulfonamides Treatment for true ITP Prednisone 1mg/kg IVIG WinRho if Rh D positive Splenectomy Vincristine Cyclophosphamide Rituxan Romiplostim (Nplate) A word about HUS-TTP Hemolytic Uremic Syndrome-Thrombotic Thrombocytopenic Purpura Precipitated by an antibody causing excessive VWF multimers leading to excessive platelet aggregation Small vessel endothelial damage is likely precipitationg factor Platelets are used up in forming microscopic thrombi Microangiopathic hemolytic anemia as result Signs/symptoms HUS-TTP Neurological deficits—confusion, etc Renal failure Thrombocytopenia Elevated LDH Anemia Schistocytes on peripheral smear Helmet cells/burr cells on peripheral smear Purpura/petechiae HUS-TTP treatment Plasmapheresis--Plasma exchange of 40mL/kg daily until PLT > 100k and fall in LDH. Supportive care No platelet transfusion!!! Special Exam Slide HELLP syndrome – Hemolysis Elevated Liver enzymes Low Platelets – Preeclampsia/eclampsia – Recover after delivery – May need plasmapheresis Many words about DIC (disseminated intravascular coagulation) Under normal circumstances… – Tissue Factor released at site of injury – Leads to formation of thrombin at site of tissue injury – Leads to activation of platelets and coagulation cascade at site of tissue injury DIC – Leads to local thrombin->fibrinogen->fibrin plug – Plasmin eventually dissolves plug – Whole process is tightly regulated by inhibitory proteins (antithrombin, Tissue factor pathway inhibitor) DIC In DIC however.. – Tissue factor released at injury site – Leads to formation of thrombin at site of tissue injury and throughout the entire vasculature – Leads to activation of platelets/coagulation cascade throughout the entire vasculature – Leads to platelet, fibrin deposition throughout entire vasculature. DIC Plasmin, antithrombin, TFPI unable to keep up with out-of-control coagulation cascade. Results in tissue ischemia, consumption of platelets, fibrinogen, coagulation factors V and VII, prothrombin. Leads to bleeding as all components of clotting cascade used up in useless clots. DIC—but wait, there’s more! Not only does one have an out-of-control activation of the clotting cascade in DIC but there is also a second component. DIC-Fibrinolysis Eventually, plasminogen makes plasmin and the widespread fibrin clots begin to break down – Releases fibrin split (degradation) products – FSP enhances bleeding by inhibiting platelet aggregation – Plasmin also breaks down remaining circulating clotting factors and fibrinogen worsening bleeding even more. DIC labs So, lab values should show both a consumptive bleeding diathesis AND a fibrinolytic process. – prolonged PT (intrinsic pathway/PTT (extrinsic pathway) – Low fibrinogen (it’s being used to make fibrin) – Low platelets – Elevated FSP/D-dimer – Low antithrombin DIC—why? Release of tissue factor into circulation Extensive vascular endothelial injury exposing tissue factor Enhanced release of tissue factor by monocytes in response to various cytokines/endotoxins. DIC-Why? Infections—bacterial/viral – Acute uncompensated DIC Malignancy—Trousseau’s syndrome (chronic compensated DIC) – More thrombotic than bleeding Aortic aneurysms/hemangiomas Abruptio placentae/retained dead fetus Trauma DIC-Why? Snake bites Heat stroke HELLP DIC signs/symptoms So patients with DIC should show signs/symptoms leading to release of tissue factor and the resultant widespread thrombus formation and bleeding diathesis. DIC signs/symptoms Bleeding—from everywhere Septic shock Renal failure Respiratory failure—pulmonary hemorrhage/ ARDS Hepatic dysfunction CNS changes Evidence of cancer/acute promyelocytic leukemia DIC-Treatment Underlying cause Plasma transfusion ? Platelet transfusion—only if severe bleeding? ? Heparin to promote antithrombinthrombin binding. ? Antithrombin infusion Thrombocytopenia due to impaired production Invasion of marrow by malignant cells Bone marrow hypoplasia – Due to chemo, drugs Chloramphenicol, gold, phenytoin, sulfonamides Thrombocytopenia due to impaired production Treatment – Platelet transfusions – Treat underlying cause – Hold offending drug – Amicar—plasmin inhibitor Thrombocytopenia due to abnormal distribution Hypersplenism – Normally 30% of platelets reside in the spleen – In cases of splenomegaly the spleen will sequester more platelets, resulting in a decrease in circulating platelets – Caused by portal hypertension/lymphoma Thrombocytopenia due to abnormal distribution Treatment of hypersplenism: – Splenectomy – Remember to vaccinate for encapsulated organisms prior to splenectomy Cases 1. So, 35 y/o female truck driver presents to outpatient clinic with bruises. Cases 2. 55 y/o male in ED s/p MVA with multiple open fractures. Postoperatively develops PLT 15k, bleeding from everywhere. Cases 45 y/o female teacher admitted with plt count 20.