This document provides definitions and information about thrombocytopenia (platelet count <150,000/ml). It discusses increased bleeding risk with very low platelet counts and common clinical presentations. Potential causes of thrombocytopenia include decreased platelet production, increased platelet destruction, dilutional effects, and pseudothrombocytopenia. Specific conditions covered in detail include immune thrombocytopenic purpura, heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Evaluation, diagnosis, and treatment approaches are outlined for the different conditions.

1. Diana Girnita, MD, PhD
The Christ Hospital
December 2011

2. Definition
 Platelets < 150,000/ml
 2.5% of normal people < 150,000/ml
 Recent drop ≥ 50%, even if normal platelets
count

3. Increased risk of bleeding
if < 60,000 -with minor trauma
if < 12,000 –spontaneous
If < 6,000 - severe, life threatening

4. Initial approach of the patient
 Clinical:
1. epistaxis
2. gingival bleeding
3. meno/ metrorrhagia
4. tend to bleed immediately after minor trauma
5. cerebral bleeding
 Cutaneous: petechiae, purpura, ecchymoses

5. Clinical presentation
A: Dense, cutaneous petechiae on the foot and ankle. B:Bullous hemorrhages on the
buccal mucosa
PURPURA - purplish discoloration of the skin due to the presence of confluent petechiae
Ecchymoses — nontender areas of bleeding into the skin, usually associated with
multiple colors

6. PMH
?Bleeding history
?Hematologic disease (acute /chronic leukemias,
MDS)
?Recent new drugs or drugs that are only taken
intermittently (ASA, NSAID, herbal, plavix, heparin)
?Recent live virus vaccination
?Recent infection (viral, bacterial, rickettsial) /sepsis
?Recent travel — malaria /dengue virus,
leptospirosis, meningococcemia, hantavirus,
hemorrhagic fevers (eg, Ebola, Lassa ).

7. PMH- cont
?Recent massive transfusion (PRBCs /platelets)
in an allo-sensitized recipient
? Recent organ transplantation by sensitization to
platelet allo-antigens /GVHD
?Pregnancy especially late in the 3rd trimester or at
onset of labor , +/- ITP or TTP-HUS, or
preeclampsia/ eclampsia
FH: ++ for bleeding and/or thrombocytopenia

8. The physical examination
 Examination in critical areas
1. Ocular fundus -CNS bleeding
2. Lymphadenopathy
3. Hepatosplenomegaly
4. Stool for occult blood
5. Skin -feet and ankles , presacral area, areas of
previous trauma
 Outline areas of bleeding with a marking pen (changes
in the number/pattern of petechiae)

9. Labs
 CBC -WBC, RBC, Plt count -r/o TTP and acute leukemia
 PERIPHERAL SMEAR
 Plt #
 Ptl morphology- large?
 +/- Plt clumping
 +/- scystocytes
 If anemia: ? Hemolytic ?
 (LDH, haptoglobin, Bilirubin)

10. Bone marrow examination
 Evaluate megakariocytes
 BM could be
 Hypocellular
 Cellular
 BM replacement

11. Mechanisms of thrombocytopenia
1. Pseudothrombocytopenia
2. Decreased platelet production
3. Increased platelet destruction
4. Dilutional thrombocytopenia
5. Distributional thrombocytopenia

12. Pseudothrombocytopenia
 EDTA-induced platelet clumping
 Drugs –Abciximab -
directed against the
GP IIb/IIIa receptor

13. Decreased platelet production
 Hypocellular BM
 Infections (MMR,
varicella, parvovirus,
hepatitis C EBV, HIV,
rickettias)
 Live attenuated
vaccines
•Drugs
•Aplastic anemia
•Alcohol
•Autoantibody -
against the
thrombopoietin
receptor (SLE)

14. Decreased platelet production
 Cellular BM
 Leukemias
 MDS
 Severe vit B12 /folate deficient anemia
MDS

15. Decreased platelet production
 Marrow replacement
 Myelofibrosis
 Solid malignancies
 Granulomas
Myelofibrosis

16. Increased platelet destruction
1.Immune –mediated
 Primary ITP
 Secondary: infectious, CLL, drugs (heparin), APL sdr,
lymphoma
 Allo-immunization (post-transfusion)
2. Non-immune mediated
 MAHA (TTP-HUS, DIC)
 Evan Sdr: thrombocytopenia + hemolytic anemia
 Vascular prostheses/ bypass; trauma
 Drugs: ticlopidine/clopidogrel,
 Cavernous hemangioma
 HELLP syndrome -in pregnant women

17. Other causes:
 Dilutional thrombocytopenia — massive blood transfusion
with PRBC (> 20 units of PRBCs /24H)
 Distributional thrombocytopenia caused by splenic
sequestration
Portal hypertension
Cirrhosis
Splenomegaly
Hypothermia

18. Thrombocytopenia in the ICU patient
 Sepsis/septic shock - one-half of the cases
 Use of heparin
 DIC
 Massive blood transfusion
 Post-transfusion purpura
 Cardiopulmonary resuscitation
 Cardiopulmonary bypass
 ARDS
 PE
 Use of intravascular catheters
 Solid organ allograft rejection
 Drugs (antibiotics, chemotherapy, antiplatelet agents -
abciximab)

19. Heparin induced thrombocytopenia
(HIT)
HIT I
HIT II

20. HIT II
 an immune-mediated disorder characterized by the
formation of antibodies against the heparin-platelet
factor 4 complex.
 UFH/LMWH
 5-10 days after the heparin is started
 Heparin –PF4 complex- Ab induce platelet aggregation
and activation, endothelial cell activation (IL-6, vWF)
 Thrombosis (arterial and venous) + thrombocytopenia
(>50% fall in Plt)
 DVT, PE (25%)
 Skin necrosis at injection site

21. Dg of HIT II
 Serotonin release assay
 Heparin-induced platelet aggregation
 The solid phase ELISA immunoassay- heparin-PF4-
IgG antibodies

22. Treatment HIT II
 Stop the heparin UFH/LMWH
 Lepirudin — Refludan®
 Is a recombinant hirudin (anticoagulant action, similar to
antithrombin III - the thrombin inhibitor)
 For HIT complicated by thrombosis, preventing new thromboses
 Not for renal failure patients
 Argatroban
 Is a direct thrombin inhibitor
 Metabolized in the liver
 Activity monitored by APTT
 Good for renal failure patients
 Warfarin — when
1) patient stably anticoagulated with a thrombin-specific inhibitor
2) Plt > 150,000/microL

23. Challenges in bridging to long term
anticoagulation
 The combination of argatroban and warfarin may raise
the INR > 5.0 without a significant increased risk of
bleeding complications.
 Measure the chromogenic factor X level
 A level < 40-45% typically indicates that the INR will
be therapeutic (2-3) when the argatroban is
discontinued.

24. HIT I
 Non-immune mechanism, appears to be due to a
direct effect of heparin on platelet activation
 1-4 days after heparin is started
 Platelets in the 100.000/mm3 range
 No thrombotic events
 No hemorrhage
 Management : observation

25. HIT I vs HIT II

26. Thrombotic thrombocytopenic purpura-
hemolytic uremic syndrome (TTP-HUS)
 Thrombocytopenia
 Microangiopathic hemolytic anemia
 Neurologic symptoms and signs
 Renal function abnormalities
 +/- Fever
 TTP-HUS is associated with thrombi composed
primarily of platelets in affected organs

27. Etiology TTP
 ADAMTS13 deficiency (vWf-cleaving protease) —leads
sequentially to the accumulation of unusual large vWf
multimers, platelet aggregation, and the platelet
clumping
 Genetic
 Acquired: DIC, HSCT, chemotherapy, severe sepsis, SLE,
leukemia, acute inflammatory states, cirrhosis, uremia,
drugs (ticlopidine, clopidogrel, quinine)

28. Etiology HUS
 Enterohemorrhagic E coli
 Shiga toxin binds and activates endothelial cells and
platelets and induces formation of intra-renal thrombi
Clinic:
 Children
 Bloody diarrhea
 Fever

29. Diagnosis TTP-HUS
 Peripheral smear: ++ Schystocytes
 Negative Coombs test
 Normal PT, PTT, fibrinogen
 Hemolysis : LDH increased (tissue ischemia +
hemolysis), indirect bilirubin increased, decreased
haptoglobin
 Increased creatinine
 Biopsy: arterioles filled with hyaline thrombi (DDx:
vasculitis, DIC, HELLP, malignant HTN)

30. Treatment TTP-HUS
1. Plasma exchange
Exceptions:
 Postdiarrheal HUS in children
 Cancer chemotherapy or transplantation
 Severe acute renal failure- cause fluid overload
2. Glucocorticoids: severe deficiency of ADAMTS13
Platelet transfusions are contraindicated

31. Immune thrombocytopenic
purpura (ITP)
 Dg of exclusion
 ITP is related to a combination of
 increased platelet destruction along with
 inhibition of megakaryocyte platelet production via the
production of specific IgG autoantibodies directed
against platelet membrane GP (GPIIb/IIIa)

32. Diagnosis ITP
 CBC : ITP+AIHA = Evans Sdr
 Peripheral smear: large platelets
 Bone marrow aspirate >60 yo to r/o MDS
 Antiplatelet antibody testing –not recommended by
the ASH
 Platelets have HLA A, B-testing for anti-HLA ab to
match platelets
 Consider ANA, viral serologies, H pylory Ab

33. Treatment ITP
 Initial :
 Steroids: PDN/ methylprednisolone (bleeding)
 IVIG
 WinRho (AntiRh-D) in Rh positive pt; ab coated RBC
overwhelm Macrophages Fc receptor
 Refractory
 Splenectomy
 Rituximab (anti-CD20)
 Azathioprine, Cyclophosphamide
 Thrombopoiesis stimulant: Eltrombopag

34. References
 www.uptodate.com
 John Hopkins IM board review
 PG MGH handbook

35. Thank you!
ALYSA & ANA