Approach to thrombocytopenia.pptx
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above. During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach. Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis. So, summarizing, in the evaluation of a case of thrombocytopenia, all the
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Approach to thrombocytopenia.pptx
- 1. Diagnostic approach to Thrombocytopenia Dr Pritish Chandra Patra Associate Professor Dept. of Clinical Hematology, Hemato-Oncology & Stem Cell Transplant IMS & SUM Hospital, Bhubaneswar
- 2. A normal platelet count • 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 a low 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 to diagnosis Detailed history Physical examination Lab investigation
- 6. 1st step: Rule out 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 platelet indices Platelet indices MPV PDW P-LCR IPF By automated hematology analyzers Large platelet
- 8. Thrombocytopenia- approach to diagnosis 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/increased number 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)
- 12. Case studies
- 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 • 65 yr 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- CLPD panel- 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 • 5 yr 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 • 30 yr 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 promyelocytic leukemia (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 • 60 yr 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- aplastic anemia/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 • 50 yr 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
- 25. Summary
- 26. Thank You