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Platelet disorders
- 2. Primary vs Secondary Hemostasis Primary Hemostasis • Formation of weak platelet plug Secondary Hemostasis • Stabilization and strengthening of platelet plug
- 3. Primary Hemostasis Platelet GP1b receptor GP2b/3a receptor Endothelium Steps: 1. Adhesion 2. Degranulation 3. Aggregation
- 4. Primary Hemostasis Adhesion: • Platelets bind vWF using GP1b receptor
- 5. ADP ADP ADP A2 A2 A2 Primary Hemostasis Degranulation: • Adhesion leads to change in shape of platelet • Degranulation of ADP and Thromboxane A2 occurs o ADP release leads to change in configuration of GP2b/3a
- 6. Primary Hemostasis Aggregation: • GP2b/3a receptor binding via fibrinogen bridge forms weak plug
- 7. How to stop aow to stop a
- 8. • Irreversible blockade of ADP receptors – Clopidogrel – Prasugrel – Ticagrelor – Ticlopidine • G2b/3a binders – Abciximab – Eptifibatide – Tirofiban
- 10. Issues with Primary Hemostasis Clinical presentation: – Epistaxis – Gingival bleeding – GI bleeding – Hemoptysis – Petechiae – Purpura – Hematuria – Menorrhagia
- 11. Issues with Secondary Hemostasis Clinical presentation: • Deep tissue bleeding o Hemarthrosis o Hematoma
- 14. Definition • Thrombocytopenia is defined as platelets < 150,000 microL – Mild 100,000 – 150,000/microL – Moderate 50,000 – 100,000/microL – Severe < 50,000/microL
- 17. True thrombocytopenia? • Recheck platelet count, check peripheral smear for clumping – EDTA decreases calcium content platelet clumping – Use Sodium citrate (blue top) or Heparin (green top) tube instead • If truly thrombocytopenic, assessment of: – Hep C, HIV, and TSH are helpful • Both hyper and hypothyroidism can cause thrombocytopenia
- 18. Partial list of medications known to cause thrombocytopenia • Abciximab • Beta-Lactams • Carbamazipine • Eptifibatide • Gold compounds • Heparin • Linozolid • MMR vaccine • Phenytoin • Pipercillin • Quinidine • Quinine • Rifampin • Sulfonamides • Tirofiban • Bactrim • Valproic acid • Vancomycin https://www.cfhi-fcass.ca/sf-images/default-source/cartoons-copyright/DrugSafe-EN.jpg?sfvrsn=0
- 20. Idiopathic Thrombocytopenia Purpura Pathology: • IgG against platelet antigens (i.e. GPIIb/IIIa) • Splenic macrophages consume antibody bound platelets – Association with CLL and non Hodgkins lymphoma Presentation: • Typically female • Purpura and thrombocytopenia. – Usually isolated thrombocytopenia without other causes • Diagnosis of exclusion Diagnosis: • Lab tests show low platelets usually <50,000K • Normal PT/PTT, smear normal Treatment: • Steroids +/- IVIG • Rhogam for Rh+ • Rituximab • Splenectomy
- 22. Microangiopathic hemolytic anemia (TTP, DIC, etc.)
- 23. Thrombotic Thrombocytopenic Purpura Pathology: • ADAMSTS-13 deficiency accumulation of clumps of large vWF multimers bind to masses of platelets microvascular occlusion and thrombocytopenia Presentation: • Febrile • Anemia • Thrombocytopenia • Renal dysfunction • Neurological findings Diagnosis: • MAHA on peripheral smear • Normal fibrinogen, d-dimer, and factor levels • ADAMSTS-13 has poor sensitivity – Treat when you have high suspicion Treatment: • Plasmapheresis
- 24. Hemolytic Uremic Syndrome Atypical HUS • Antibodies to Complement Factor H – Atypical HUS is complement mediated and usually NOT proceeded by diarrhea. • Eculizumab is treatment of choice Secondary • Infection related – Classical version associated with diarrheal illness elaborating Shiga Toxin (Escherichia Coli O157:H7 in the USA) – O118:H2, O111:H or O104:H4 in Europe and other regions around the world – Strep Pneumo – HIV in children • Drug toxicity particularly those with cancer or solid organ transplants • Treat with plasmapheresis
- 25. Disseminated Intravascular Coagulation Pathology: • Severe underlying disease – Pancreatitis, sepsis, malignancy (especially APML), cirrhosis, TRALI, obstetrical complications like preeclampsia or retained dead fetus Presentation: • Bleeding/oozing Diagnosis: • MAHA on peripheral smear and low platelets • Low fibrinogen, increased d-dimer, increased PT/PTT, INR Treatment: • Treat the underlying condition • Transfuse – Thrombocytopenia – Low fibrinogen (Cryoprecipitate) – Prolonged PT/PTT (FFP) – Anemic
- 29. Heparin Induced Thrombocytopenia Pathology: • Drug-induced thrombocytopenia in which the antigen is a complex between platelet factor 4 (PF4) and heparin • Antibodies directed against the heparin/PF4 complex can activate platelets via Fc receptors on platelets, leading to thrombocytopenia and, paradoxically in some patients, thrombosis Presentation: • Drop in platelets 5-10 days after heparin initiation • Thrombosis Diagnosis: • 4Ts Score • Elisa for anti-PF4 antibodies (Sensitive – in house – high number of False Positives). Checking for optical density <0.4 or >2.0 • Serotonin Release Assay (Specific – send out test) Treatment: • Stop heparin • Agatroban for renal dysfunction and normal hepatic function • Fondaparinux for hepatic dysfunction and normal renal function • Agatroban or Bivalirudin at reduced dosage if both renal and hepatic dysfunction • Warfarin should not be started until platlet count normalizes due to risk of warfarin skin necrosis
- 33. Citations • https://www.uptodate.com/contents/management-of-heparin-induced- thrombocytopenia?source=see_link • https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-heparin- induced-thrombocytopenia?source=search_result&search=HIT&selectedTitle=1~150 • https://en.wikipedia.org/wiki/Megakaryocyte • Fauci, A. S., & Harrison, T. R. (2008). Harrisons principles of internal medicine. New York: McGraw-Hill, Medical Publishing Division. • Le, T., & Bhushan, V. (2013). First aid for the USMLE step 1 2013: a student to student guide. New York: McGraw-Hill Medical. • https://onlinemeded.org/hematology-oncology/bleeding • Sattar, H. A. (2017). Fundamentals of pathology: medical course and Step 1 review. Chicago, IL: Pathoma.com. • Master the Boards Step 2 CK • MKSAP 17
Editor's Notes
- Adhesion: at sites of endovascular injury vWF adheres to subendothial collagen. Platelets bind vWF using GP1b receptor Degranulation: adhesion changes shape of platelets leading to degranulation of ADP and ThromboxaneA2 which promote aggregation Aggregation: Aggregation via GP2b/3a receptor via fibrinogen bridge forms weak platelet plug Endothelin – vasoconstriction Nitric oxide and prostaglandins – vasodilation and inhibition of GP1b function
- Adhesion: at sites of endovascular injury vWF adheres to subendothial collagen. Platelets bind vWF using GP1b receptor Degranulation: adhesion changes shape of platelets leading to degranulation of ADP and ThromboxaneA2 which promote aggregation Aggregation: Aggregation via GP2b/3a receptor via fibrinogen bridge forms weak platelet plug
- Adhesion: at sites of endovascular injury vWF adheres to subendothial collagen. Platelets bind vWF using GP1b receptor Degranulation: adhesion changes shape of platelets leading to degranulation of ADP and ThromboxaneA2 which promote aggregation Aggregation: Aggregation via GP2b/3a receptor via fibrinogen bridge forms weak platelet plug
- Adhesion: at sites of endovascular injury vWF adheres to subendothial collagen. Platelets bind vWF using GP1b receptor Degranulation: adhesion changes shape of platelets leading to degranulation of ADP and ThromboxaneA2 which promote aggregation Aggregation: Aggregation via GP2b/3a receptor via fibrinogen bridge forms weak platelet plug
- Platelet clumping signifies pseudothrombocytopenia, which will resolve if blood is redrawn using a citrated or heparinized tube. EDTA issues – decreased calcium.
- Thrombotic thrombocytopenic purpura is a clinical diagnosis that requires the presence of thrombocytopenia and microangiopathic hemolytic anemia, which is confirmed by schistocytes on the peripheral blood smear.
- Thrombotic thrombocytopenic purpura is a clinical diagnosis that requires the presence of thrombocytopenia and microangiopathic hemolytic anemia, which is confirmed by schistocytes on the peripheral blood smear.
- https://iowagenetics.files.wordpress.com/2008/09/slide5.jpg
- Cryo – made from FFP which is frozen and repeatedly thawed to produce a concentrated source of clotting factors including Factor VIII, vWF, Fibrinogen (Factor I) FFP – Just plain old plasma
- Assessing the pretest probability of heparin-induced thrombocytopenia by using a risk scoring system, such as the 4T score, is helpful in guiding therapy in patients at low risk for it. This patient gets 0 points. <30% drop, <4 days, no thrombosis
- Heparin cessation and immediate treatment with a nonheparin alternative anticoagulant (lepirudin, argatroban, danaparoid) are mandatory when a high pretest probability of heparin-induced thrombocytopenia is present.
- ≤3 points: low probability for HIT (≤5% in original study, <1% in meta-analysis). 4-5 points: intermediate probability (~14% probability of HIT). 6-8 points: high probability (~64% probability of HIT).
- Bernard Soulier – BS – BIG SUCKERS
- https://www.pinterest.co.uk/pin/115967759132892978/