1. Approach to Thrombocytopenia
Usha Perepu, MD
Assistant Professor, Internal Medicine
4/18/2017

2. Disclosure
No conflicts of interest associated with this presentation

3. Learning Objectives Understand the platelet biology and its function
Importance of history taking in a patient with thrombocytopenia
Identify the common causes of thrombocytopenia and their management

4. Platelet Biology
Platelets are normally produced in the bone marrow from progenitor cells known as megakaryocytes
Production stimulated from thrombopoietin
Platelet life span: 7-10 days
Clearance via macrophages in the RE system
25-35% of platelets located in the spleen
Young platelets more active than older platelets
Normal platelet count is between 150,000 and 450,000/µL

5. Platelet Function
PLATELET ACTIVATION

6. Concern for Bleeding
In the absence of qualitative platelet dysfunction:
>100,000/µL--no increased risk of bleeding
50,000 to 100,000/µL--possible increased risk of bleeding with major trauma or surgery
10,000 to 50,000/µL--increased risk of bleeding with minor trauma or surgery
<10,000/µL--increased risk of spontaneous life-threatening bleeding

7. History and Physical Examination
Prior platelet counts
History of bleeding
Infections, other medical conditions
Diet
Drug history
Family history
PE: organomegaly, site of bleeding, evidence of thrombosis
New onset, chronic, or relapsing.
Disease history with particular reference to autoimmune disorders, infections, malignancies, pregnancy, recent medications and vaccines. Travel ( malaria, rickettsia, dengue fever).
Recent transfusions, organ transplantation
Alcohol, quinine containing beverages
Dietary habits
Questions to think about
Is the patient bleeding?
Do the sites of bleeding suggest a platelet defect?
Duration- is thrombocytopenia- acute or chronic?
Is there a history of medications, alcohol use or recent transfusion?
Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease)
Heparin exposure- recent of within the past 3 months?
Are there risk factors for HIV infection?
History of liver disease
Is there a family history of thrombocytopenia?

8. Laboratory Testing CBC: Peripheral blood smear
isolated thrombocytopenia
Combined anemia and thrombocytopenia
Leukocytosis
Peripheral blood smear
Clumps: Pseudothrombocytopenia
Schistocytes: microangiopathic process
Leukoerythroblastic picture: bone marrow infiltration
Hypersegmented neutrophils: ? B12 deficiency
Liver function tests, renal function, coagulation profile, nutrient workup (B12 , folate), viral infections (HIV hepatitis), autoimmune workup, bone marrow biopsy
Peripheral blood smear still remains the most important investigation guiding our diagnostic approach to thrombocytopenia

9. Causes of Thrombocytopenia
Decreased production
Increased destruction /consumption
Sequestration
Intoxication ( alcohol)
Immune thrombocytopenia
Portal hypertension
Viral infections (HIV, HCV, EBV, CMV)
Thrombotic microangiopathy
Infiltrative diseases of the spleen
Bone marrow infiltration( leukemia, tumors etc)
Post transfusion purpura
Radiation/chemotherapy
Drug induced ( heparin, quinine etc)
Drug induced
Nutrient deficiencies (B12, folate, copper)
DIC/trauma
Hereditary
Cardiopulmonary bypass
Several causes
Can be broadly classified into five categories
Pseudo or spurious thrombocytopenia
Dilutional
Decreased production
Increased destruction
Altered distribution (increased sequestration)

10. Hematology Am Soc Hematol Educ Program. 2012;2012:191-7.

11. Thrombocytopenia in Pregnancy
Very common in pregnancy: ~5-10%
The most common causes are:
Gestational thrombocytopenia (70%)
Preeclampsia (21%)
ITP (3%)

12. Gestational Thrombocytopenia
Etiology:
– Dilutional
– decreased platelet production
– Increased platelet turnover
Occurs later in pregnancy
Usually mild thrombocytopenia, >70,000/µL
Diagnosis of exclusion……but so is ITP
Not associated with adverse events
Resolves 1-2 months after delivery
Treatment not usually required

13. Immune Thrombocytopenia (ITP)
Children: acute, self-limited
Adults: chronic
Severe thrombocytopenia due to anti-platelet antibodies
Normal or increased numbers of megakaryocytes in bone marrow
May be associated with other autoimmune disorders
Treated with corticosteroids, IVIG or anti-D immunoglobulin, splenectomy, or rituximab (anti-CD20 monoclonal antibody)
Thrombopoietin (TPO) receptor agonists
IVIG increases the platelet count by interfering with macrophage uptake of autoantibody-coated platelets (ie, "overwhelming" the reticuloendothelial system)

14. Thrombotic Thrombocytopenic Purpura (TTP)
Syndrome of thrombocytopenia, fever, acute renal insufficiency, CNS dysfunction, and microangiopathic hemolytic anemia
Many cases caused by deficiency of vWF-cleaving protease (ADAMTS13)
Schistocytes and elevated LDH
PT and APTT are usually normal
TTP is a medical emergency that is often fatal if not treated urgently with plasma exchange

15. Hemolytic Uremic Syndrome (HUS)
Variant of TTP
Predominant renal involvement
Often associated with pathogenic E. coli harboring a plasmid encoded Shiga toxin
Leading cause of renal failure in children worldwide
Not caused by deficiency of ADAMTS13
Treatment is supportive

16. Drug Induced Immune Thrombocytopenia
Several drugs are known to cause thrombocytopenia
Mechanism: development of drug dependent Abs against new epitopes of platelet glycoproteins created by their interaction with the drug
Presents with moderate to severe thrombocytopenia
2-3 days after drug exposure
Resolves spontaneously in 5-10 days after drug discontinuation
Can be confused with ITP

18. Heparin Induced Thrombocytopenia
Occurs in 0.5-5% of heparin treated subjects
Develops 5-10 days after heparin exposure
Antiplatelet Abs cause platelet activation, resulting in increased risk of thrombosis
Thrombocytopenia is moderate around 50,000-80,000/µL, rarely < 20,000/µL
> 50% drop in platelet count while on heparin
Management: calculate 4T score, discontinue heparin and consider alternate anticoagulation, heparin PF4 Ab testing

19. Algorithm for Workup of Thrombocytopenia
Hematology Am Soc Hematol Educ Program. 2012;2012:191-7.