Platelets Flashcards
Quantitative platelet disorders
Thrombocytopenia and thrombocytosis
Qualitative platelet disorders
Abnormal platelet function
Thrombocytopenia
A disorder in which there is a relative decrease of platelets present in blood, normal count is 150,000 to 450,000 platelets per microliter
Clinical features of thrombocytopenia
Easy bruising, petechiae, prolonged bleeding, bleeding from gums or nose, blood in urine and stools, heavy menstrual flows, fatigue, enlarged spleen, jaundice
Lab tests for abnormal bleeding
Platelet count, PT, APPT, bleeding test
Thrombocytopenia causes
Decreased production, increased destruction, sequestration, pseudothrombocytopenia, dilutional thrombocytopenia
Pseudothrombocytopenia
Artifactually low platelet count due to in vitro clumping of platelets, usually caused by antibodies that bind platelets only in presence of EDTA, seen in healthy individuals and in many disease states
Diagnosis of pseduothrombocytopenia
Marked fluctuations in platelet count, thrombocytopenia disproportionate to symptoms, clumped platelets on smear, Platelet satellites, abnormal platelet/leukocyte histograms, platelet count varies with different anticoagulants
Platelet satellitism
IgG antibody coats platelets, platelets rosette around segs, bands, and sometimes monocytes, if huddled around WBCs, not counted by automation, causing false decrease
Dilutional thrombocytopenia
Large quantities of PRBC transfusion to treat massive hemorrhage can lead to dilution TP, due to absence of viable platelets in packed RBCs, usually platelet counts in patients receiving 15 to 20 units of PRBCs in 24 hours in 50k to 100k, can be prevented by giving platelets
Decreased platelet production
Marrow failure, B-12, folate or iron deficiency, viral infection, drugs, amegakaryocytic thrombocytopenia, cyclic thrombocytopenia, inherited thrombocytopenia
Thrombocytopenia and ppregnancy
Benign thrombocytopenia of pregnancy, occurs in 5% of term pregnancies, accounts for ~ 75% of cases of thrombocytopenia, asymptomatic, mild, occurs late in gestation, microangiopathy, ITP
Increased platelet consumption
Immune destruction, non-immune destruction
Non-immune mechanisms of destruction
Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, mechanical destruction by artificial heart valves
Immune platelet destruction
Autoimmune (ITP), drug-induced (heparin, Quinine), Immune complex (infection), Alloimmune (post-transfusion purpura, neonatal purpura)
Post-transfusion purpura
caused by re-exposure to foreign platelet antigen via blood transfusion, almost all cases in multiparous women, antibodies cause destruction of patient’s own platelets by uncertain mechanism, typically presents as sudden onset of severe thrombocytopenia 5-7 days after transfusion
Neonatal alloimmune thrombocytopenia
Maternal alloantibodies against a platelet antigen (HPA 1a and 1b), symptoms appear at or shortly after birth and are self limited, rarely high mortality due to CNS bleeding
Thrombocytopenia and infection
Immune complex-mediated platelet destruction, activation of coag cascade, vascular/endothelial cell damage, damage to platelet membrane components by bacterial enzymes, decreased platelet production, mixed production defect/immune consumption
ITP childhood form
most < 10 years old), may follow viral infection or vaccination, peak incidence in fall and winter, ~50% receive some treatment, >75% in remission within 6 months
ITP adult form
No prodrome, chronic, recurrences common, spontaneous remission rate ~5%
ITP adult apidemiology
1-10/100,000, slightly more common in women, about 40% have an associated disorder
ITP peak age
Children: 2-4 years
Adults: 20-40 years
ITP platelet count
Acute: <20 x 10^9/L
Chronic: 30-80 x 10^9/L
ITP Onset
Acute: Abrupt
Chronic: Insidious
ITP antecedent infection
Acute: Common - 1-3 weeks
Chronic: Unusual
ITP spontaneous remission
Acute: ~93%
Chronic: Rare, course of disease fluctuates
ITP therapy
Acute: corticosteroids, Anti-D, IVIg
Chronic: Corticosteroids, splenectomy
ITP management in children
Platelets > 20-30K, no bleeding = no Rx
Platelets <10K or <20K with significant bleeding = IVIg or corticosteroids
Splenectomy reserved from chronic ITP or refractory disease with life-threatening bleeding
ITP in pregnancy
Mild cases are indistinguishable from gestational thrombocytopenia, rule out eclampsia, treatment if IVIg, splenectomy for severe, refractory disease, potential for neonatal thrombocytopenia
Thrombotic microangiopathies
Presence of hemolytic anemia, low platelets, and organ damage due to formation of microscopic blood clots in capillaries and small arteries
Thrombotic microangiopathies causes
infection, medications, connective tissue diseases, cancer, vasculitis, pregnancy, malignant hypertension, organ transplant, and metabolic disorders
Thrombotic thrombocytopenic purpura presentation
abdominal pain, nausea, vomiting, weakness, 1/2 will have neurologic abnormalities
The pentad for TTP
Microangiopathic hemolytic anemia, thrombocytopenia often with purpura, acute renal insufficiency, neurologic abnormalities, fever
Causes of TTP
Idiopathic, drug-associated, autoimmune disease, infection, pregnancy/postpartum, bloody diarrhea prodrome, hematopoietic cell transplantation
ADAMTS13 deficiency
VWF-cleaving protease, normally cleaves long VWF multimers secreted by endothelial cells, without ADAMTS13, long stick VWF multimers accumulate, react with platelets and cause formation of disseminated platelet thrombi
Testing for ADAMTS13 deficiency
Assay techniques, severe deficiency predicts an increased rick of relapse
Testing for ADAMTS13 deficiency
Assay techniques, severe deficiency predicts an increased risk of relapse
HUS symptoms
Diarrhea, vomiting, urine output reduction, neurologic symptoms, typically follows GI infection
Disseminated intravascular coagulation (DIC) causes
Excess tissue factor and endothelial damage, activation of fibrinolysis, other procoagulant or profibrinolytic substances
Complications of DIC
bleeding, thrombosis, tissue necrosis
Causes of bleeding in DIC
Clotting factor consumption, high levels of FDP, endothelial damage, increased fibrinolytic activity
Thrombosis in DIC
Large vessel thrombosis is uncommon, more common in chronic DIC, clots may form around intravascular catheters
Contributing factors of tissue necrosis and DIC
intravascular fibrin, endothelial damage, downregulated fibrinolysis, hypotension, pressor administration, acquired protein C deficiency
Protein C
Physiological anticoagulant, Vitamin K dependent, destroys factors Va and VIIIa, activated by thrombin bound to endothelium, protective effect on endothelium, severe deficiency of protein C can cause tissue necrosis
Protein C
Physiological anticoagulant, Vitamin K dependent, destroys factors Va and VIIIa, activated by thrombin bound to endothelium, protective effect on endothelium, severe deficiency of protein C can cause tissue necrosis
DIC summary
Excess tissue factor + flowing blood = DIC, inflammatory cytokines set the stage for DIC and contribute to tissue damage, excessive fibrinolysis associated with higher bleeding risk, acquired protein C deficiency associated with high risk of tissue necrosis/purpura
DIC summary
Excess tissue factor + flowing blood = DIC, inflammatory cytokines set the stage for DIC and contribute to tissue damage, excessive fibrinolysis associated with higher bleeding risk, acquired protein C deficiency associated with high risk of tissue necrosis.purpura
Diagnosis of DIC
Platelet count, increased fibrinogen degradation products
Thrombocytosis cause essential
primary, other myeloproliferative disorders
Thrombocytosis cause reactive
Secondary, inflammation, surgery, hyposplenism, asplenia, hemorrhage and/or iron deficiency
Criteria for essential thrombocytosis
Platelet > 450K, megakaryocytic proliferation with large, mature morphology and with little granulocytic or erythroid expansion, not meeting other myeloid criteria, demonstration of JAK2V617F or other clonal marker or lack of evidence of a secondary
