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.

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