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Approach to thrombocytopenia.pptx
The document provides information on evaluating and diagnosing thrombocytopenia, including: 1) Normal platelet counts range from 150,000-450,000/microL and are slightly higher in females and younger people. Thrombocytopenia is defined as a platelet count below 150,000/microL. 2) The basic mechanisms of thrombocytopenia include decreased platelet production, ineffective production, increased destruction, increased consumption, and sequestration. 3) Diagnosing thrombocytopenia involves ruling out pseudothrombocytopenia, examining the blood counts, bone marrow, and performing additional lab tests to determine the underlying cause and guide treatment.
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Approach to thrombocytopenia.pptx
- 1. Diagnostic approach to Thrombocytopenia DrPritish Chandra Patra Associate Professor Dept. of Clinical Hematology, Hemato-Oncology & Stem Cell Transplant IMS & SUM Hospital, Bhubaneswar
- 2. A normal plateletcount • A study from the USA involving over 12,000 adults in the National Health and Nutrition Examination Survey (NHANES) database found the following: • Platelet count • Range from: 150,000 - 450,000/microL • Slightly higher mean values in females (266,000/microL) than males (237,000/microL) • Slightly higher in younger people than older people
- 3. What is alow platelet count? • Thrombocytopenia- defined as a platelet count below the lower limit of normal: <150,000/microL • Degrees of thrombocytopenia- further subdivided into • Mild (100,000 - 150,000/microL) • Moderate (50,000 - 99,000/microL) • Severe (<50,000/microL) • Numbers Vs underlying disease (eg, in ITP, platelet count <30,000/microL - severe thrombocytopenia) • Clinical significance- Severe thrombocytopenia (platelet count <30,000 - 50,000/microL) • greater risk of bleeding- intracranial • implies a greater likelihood for needing treatment
- 4. Thrombocytopenia: basic mechanisms Decreased platelet production(IBMFS, AA, Leukemia) Ineffective platelet production (MDS, Megaloblastic anemia) Increased platelet destruction (ITP, HLH) Increased platelet consumption (MAHA- DIC, TTP, HUS) Platelet sequestration (Hypersplenism) Combination of multiple above mechanisms
- 5. Thrombocytopenia- approach todiagnosis Detailed history Physical examination Lab investigation
- 6. 1st step: Ruleout Pseudo-thrombocytopenia • Repeat platelet count by automated cell counter • Check platelet histogram • Peripheral blood smear • Giant platelets • Platelet clumps • Platelet morphology • Large- • Bernard Soulier syndrome • Glanzmann thrombasthenia • Small- • Wiskott-Aldrich syndrome • Often reveals the etiology (e.g. Acute Leukemia) • Platelet count with non-EDTA vials • (Citrate, Heparin) • Platelet count by direct finger prick smear
- 7. Other helpful plateletindices Platelet indices MPV PDW P-LCR IPF By automated hematology analyzers Large platelet
- 8. Thrombocytopenia- approach todiagnosis Blood counts Isolated thrombocytopenia Other cell lineage cytopenia Bone marrow Megakaryocytic thrombocytopenia ? Amegakaryocytic thrombocytopenia ? Status of BM erythroid/granulocytic/lymphoid lineage ?
- 9. Lab investigations CBC, Platelet count& indices, Reticulocyte count Peripheral blood smear examination PT, aPTT, TT, Fibrinogen, D-dimer Viral markers (HIV, Anti-HCV, HBsAg) LFT, RFT, serum LDH Serum Vit-B12, Folate assay, Ferritin USG abdomen (+ spleno-portal doppler: if hypersplenism suspected)
- 10. ITP (Immune Thrombocytopenia) •Auto-immune platelet destruction • Isolated thrombocytopenia ± bleeding (mild-severe) • WBC total and differential count- normal for age • Anemia- proportionate to blood loss • No abnormal cells in PBS • Primary ITP- no organomegaly/lymphadenopathy (usually)
- 11. • BMA/Biopsy- • Normal/increasednumber of megakaryocytes • Normal morphology • Work up for secondary causes • HIV • HCV • SLE • Lymphoma (e.g. CLL) • ITP is a diagnosis of exclusion ITP (Immune Thrombocytopenia)
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- 13. Case-1 • 25yr lady •Acute onset of bleeding- spontaneous skin bruising, gum bleed, menorrhagia • No fever / bone pain • O/E- clinically stable, mild pallor, multiple ecchymoses, & purpuric spots, liver/spleen/LN- not enlarged • CBC: Plt- 10,000/cumm, Hb, TLC, DLC- normal • PBS- no abnormal cells
- 14. Diagnosis? • ITP • BMA/Biopsy-Normal • Work up for secondary ITP: Negative • 1st line treatment: Prednisolone / High-dose Dexamethasone / ± IVIG • 2nd line: Rituximab / TPO-RA (Eltrombopag/Romiplostim) • 3rd line: Azathioprine, Dapsone, MMF etc • Refractory- Splenectomy
- 15. Case 2 • 65yr old lady • Acute onset spontaneous skin bruising, gum bleed • No fever / bone pain • O/E- clinically stable, mild pallor, multiple ecchymoses & purpuric spots, liver/spleen/LN- not enlarged • CBC- Plt- 15,000/cumm, Hb- 9 g/dL, TLC- 80,000/cumm, DLC- N20 L75 M5, Retic- 8% • PBS- small mature lymphocytes, smudge cells+ • Direct Coombs Test (DCT)- Positive- 3+
- 16. Diagnosis? • Flowcytometry- CLPDpanel- s/o Chronic Lymphocytic Leukemia (CLL) • BMA+Biopsy- increased lymphoid cells, megakaryocytes increased- both mature and immature forms, no dysplasia. • Diagnosis- Evan’s Syndrome (AIHA+ITP), secondary to CLL • 1st line treatment • Corticosteroids (Prednisolone) • If no response- Rituximab ± Bendamustine
- 17. Case 3 • 5yr old girl • Acute onset of spontaneous skin bruising, epistaxis • Fever on and off x 1 month, fatigue • Look sick, febrile, pallor++, multiple ecchymoses & purpuric spots • Multiple cervical LNs, Spleen palpable 3cm • CBC: Plt- 10,000/cumm, Hb- 6 gm/dL, TLC- 25,000/cumm • PBS- Blasts- 60%, no auer rods
- 18. Diagnosis? • Acute leukemia •PB / BM- immunophenotyping- flowcytometry- B cell ALL • Cytogenetics, NGS • Treatment • Chemotherapy (pediatric ALL regimen) • Supportive treatment (with platelet transfusions)
- 19. Case 4 • 30yr old lady • Acute onset menorrhagia, spontaneous skin bruising, epistaxis, hematuria- 7 days • Decreased vision in B/L eye- 1 day • Looks sick, febrile, pallor++, multiple ecchymoses & purpuric spots, B/L sub-conjunctival hemorrhage • CBC: Plt- 5000/cumm, Hb- 6 g/dl, TLC- 5000/cumm • PBS: hypergranular promyelocytes with blasts 50% • PT, aPTT- prolonged • Fibrinogen- 40 mg/dl • D-dimer high • s/o DIC
- 20. Diagnosis? • Acute promyelocyticleukemia (APML) with DIC • Urgent transfusion- RDP / SDP + FFP + Cryoprecipitates • ATRA + ATO- to start urgently • Send from PB- RT-PCR / FISH for PML RARA • BMA + Biopsy + Cytogenetics • Continue ATRA + ATO after APML is confirmed
- 21. Case 5 • 60yr old male • Spontaneous skin bruising, gum bleed, epistaxis- 1 month • Fatigue- 3 months, h/o PRBC transfusion 4 units for anemia • Afebrile, pallor++, multiple ecchymoses, wet purpura in oral mucosa • Liver/spleen/LN- not enlarged • CBC: Plt- 10,000/cumm, Hb- 6 g/dl, TLC- 1500 (N25 L70 M5) • Retic- 0.5%, Absolute reticulocyte count- 10,000 • PBS- no blasts
- 22. Diagnosis? • D/D- aplasticanemia/MDS/acute leukemia • BMA+Biopsy+Cytogenetics+/- Flowcytometry • BMA+Biopsy- hypocellular marrow (20% cellularity), no increase in blasts, no dysplasia • Cytogenetics- 46XY • Diagnosis- Aplastic anemia • Trt- IST (ATG+Cyclosporine+Eltrombopag) • Supportive treatment- PRBC+RDP transfusions • D/D- aplastic anemia/MDS/acute leukemia • BMA+Biopsy+Cytogenetics+/- Flowcytometry • BMA+Biopsy- hypercellular marrow (70% cellularity), 3% blasts, trilineage dysplasia • Cytogenetics- 46XY, +8 • Diagnosis- MDS • Trt- • Low risk: EPO + G-CSF hypomethylating agents • High risk: Hypomethylating agents • Others (isolated 5q del)- Lenalidomide • Supportive treatment- PRBC+RDP transfusions
- 23. Case 6 • 50yr old male • Known CLD • Referred from Gastro OPD for thrombocytopenia • Afebrile, pallor+, no active bleeding • Splenomegaly 3cm • CBC: Plt- 30,000/cumm, Hb- 10 g/dl, TLC- 3500 (N65 L30 M5) • PBS- no atypical cells
- 24. Diagnosis? • ? Hypersplenism-secondary to CLD + Portal HTN • BMA+Biopsy: Normocellular marrow, normal trilineage maturation • Cytogenetics: 46XY • Trt- • Supportive • Iron and B12 replacement if deficient • Treatment of CLD & Portal HTN
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