Platelets. Released from megakaryocytes under the influence of flow in capillary sinusesNormal Platelet count1.5-4.5 Lakhs/micro liter.. . Liver -? Thrombopoetin hormone? major regulator of platelet productionIncrease in synthesis occurs with inflammation,especially with Interleukin 6 productio
1. THROMBOCYTOPENIA By DR NAGANATH NARASIMHAN PRE M
2. Platelets Released from megakaryocytes under the influence of flow in capillary sinuses
Normal Platelet count
1.5-4.5 Lakhs/micro liter.
3. Liver -? Thrombopoetin hormone? major regulator of platelet production
Increase in synthesis occurs with inflammation,especially with Interleukin 6 production.
TPO binds to receptor on platelets & megakaryocytes ? removed from circulation.
Decrease in platelets,megakaryocyte mass?increased TPO,causing platelet production.
4. Average lifespan–> 7– 10 days
One third platelets? spleen
Platelets anucleate,limited capacity to produce proteins,physiologically very active
5. Vascular endothelium injured?inhibitory effects are overcome? platelets adhere to exposed intimal surface primarily through vWF
Platelet adhesion?aggregation of intracellular signals? activation of platelet glycoprotein(Gp IIb/IIIa receptor ?platelet aggregation.
Activated Platelets? release of granules?nucleotides,adhesive proteins,growth factors,procoagulants -?serve to promote platelet aggregation,blood clot formation.
Platelet plug?stabilised by fibrin mesh.
6. Elements of hemostasis Adequate Platelet count
Adequate Platelet function: Bleeding Time
Adequate levels of Von Willebrand’s Factor
Adequate levels of Clotting Factors:Pt/INR,PTT
Adequate Blood vessel response
7. Thrombocytopenia Defined as a reduction in the peripheral blood platelet count below the normal limit of 1.5lakhs/micro liter
Reconfirmation of the platelet count should be done
Confirmation by Blood film
8. 1) Decreased bone marrow production.
(2) Sequestration, usually in an enlarged
(3) Increased platelet destruction.
9. Classification ACQUIRED
More Common Causes
Less Common Causes
10. Acquired More common causes
Idiopathic Thrombocytopenic Purpura
Aplastic Anemia Disseminated Lupus
Bone marrow infiltration—
11. Less common Infection including HIV
Megaloblastic macrocytic anaemia
Massive blood transfusion
Disseminated intravascular caogulation
12. Rare Causes Thrombotic thrombocytopenic purpura
Post partum Thrombocytopenia
Post tranfusion thrombocytopenia
13. Neonatal/congenital IMMUNE
Auto immune-mothers with chronic idiopathic thrombocytopenic purpura
Iso immune(allo immune)-platelet group incompatibility
Drug administered to mother
14. Congenital Megakaryocytic hypoplasia
Associated with congenital abnormalities/Pancytopenia
Sex linked-pure form,Aldrich’s Syndrome
15. Symptoms/signs Purpura-purple colored skin manifestations-leaked blood
Ecchymoses(purplish patch on skin),petechiae(minute hemorrhagic spots)
Depends on cause of thrombocytopenia
Most patients with platelets >50K/ul have no symptoms
Many patients live without symptoms with platelets 30-50k/ul for years
Concern for platelets<30k/ul
Especially with platelet dysfunction
Intracerebral hemorrhage <10-15K/ul
Weakness with/without blood loss
17. Signs Splenomegaly
Optic fundal hemorrhage
Prolonged bleeding from cuts
Unusually heavy menstrual flow
Prolonged bleeding during surgery
18. Approach Proper history
Whether there is easy bruising
h/o bleeding manifestations
h/o epistaxis/oral bleeding/hematemesis/hemoptysis
Overall health of the patient
h/o receiving any drugs
h/o any reduced platelets in the past
Any family history of decreased platelets
h/o ingestion of herbal drugs
19. h/o recent infections
h/o recurrent infections
Previous h/o cancers
20. Young healthy adult with thrombocytopenia—limited diagnosis
Ill hospitalized patients with multiple medications—can be difficult to diagnose
21. Physical examination Vitals should be seen
Wet purpura,blood blisters(oral mucosa)
Can be life threatening
Throat for any congestion/bleeding spots
Skin ,mucous membranes thoroughly examined
Evidence of Chronic liver disease
Other underlying disorders
Abdomen –Splenomegaly,CLD features
Per Rectal examination
Pelvic examination in females
Respiratory-to rule out any foci of bleeding
23. Thorough neurological examination should be done,to rule out any bleeding intracranially.
Fundus examination should be done.
24. investigations CBC
Hb-if there is associated anemia
WBC –to rule out any infections,if increased
Also when decreased to rule out pancytopenia if there other cell lines are also reduced
LFT-To rule out any liver disease
25. Mean platelet volume-estimates average size of platelets
26. Evaluation of platelet function Peripheral Smear –number,size,manual platelet count,Schistocytes(TTP/HUS)
Mainly measures platelet function(clot formation)
Useful for platelet counts >100K/ul
Maybe affected by fibrinogen levels.other anticoagulants
Prolonged –Uremia,liver disease
27. Bone Marrow biopsy
Number and appearance of megakaryocytes
Rapid test for antif-heparin/platelet factor 4 antibodies in development
Specific tests for different types
28. Torniquet test Performed by placing a sphygmomanometer cuff around upper arm,raising the pressure to 100mm hg for 5-7mins
If systolic pressure is <100mm hg,the pressure is raised to halfway between systolic and diastolic pressure.
2-3mins after the cuff has been deflated,the congestion disappeared,no of petechiae in an area with a 3cm diameter ,1cm below the cubital fossa is counted
29. Normal-upto 10-20
More than 20 is abnormal
In severe thrombocytopenia >100 or more
Test is positive in severe cases
Negative sometimes in mild/moderate thrombocytopenia
30. Platelet Transfusion It should be done only if the platelets go below 10,000
Life threatening hemorrhage—GI bleeding
A tranfusion is termed as successful if the bleeding manifestation for which it has been given is contolled for more than 48 hrs
31. Infection Induced Viral infections
Epstein Barr Virus
Seen in Gram negative septicemia
32. Affect Platelet production/survival
Immune Mechanisms in IMN and early HIV
Bone marrow examination-for evaluating occult infection
Required only if there is
Other non invasive methods have failed
Treatment of underlying cause of infection
33. Drug Induced Due to bone marrow suppression by T/t with lot of drugs.
In thrombocytopenia without any apparent cause,all drugs should be suspected,maybe stopped or substituted
Over the counter drugs
34. Drug dependant antibodies? specific platelet antigens-?thrombocytopenia(only when drug is present)
Induction of antibodies
Drug dependant antibodies?assays provided drug is present in assay
Occurs after period of initial exposure
And also rexposure
35. Platelet GpIIb IIIa inhibitory drug(abciximab)
Thrombocytopenia?24hrs after initial exposure
Due to antibodies that cross react with drug bound to platelet
36. Abciximab Digoxin
Aminosalicylic acid Ibuprofen
Amphotericin B Octreotide
37. Inherited Rare
Isolated/part of syndrome
Associated with mutations in non muscle myosin heavy chain MYH9 gene
May Hegglin Anomaly
Common Feature? Large Platelets
38. Autosomal Resistant Congenital Amegakaryocytic Thrombocytopenia
Thrombocytopenia with absent radii
Bernard Soulier Syndrome
Functional platelet disorder
Wiskott Aldrich Syndrome
Dyshematopoetic syndrome(mutation in transcription regulator of hematopoesis)
39. ITP Acquired disorder
Immune mediated destruction of platelets/inhibition of platelet release from megakryocytes
Adults –Chronic exact nature of immune reaction unkown
40. Secondary to
Systemic Lupus Erythematosus
Helicobacter Pylori infection
Mucocutaneous bleeding-oral.GIT,heavy menstrual bleeding
Low platelet count with normal Peripheral Smear
41. Wet purpura/Blood Blisters
Retinal Hemorrhages (life threatening bleeding)
42. LAb Bone marrow examination
Peripheral smear—large platelets
Associated iron deficiency can be present
Tests for secondary causes
Immunoglobulin levels?to r/o Hypogammaglobulinemia
43. Anemia present then
Coomb’s test to r/o Evan’s Syndrome
44. Treatment Diagnosed ITP does not mean,immediate t/t
i.e in patients without
Severe thrombocytopenia <5000/ul
Signs of impending bleeding
Rho(D)Immunoglobulin theraphy@ 50-75ug/kg
45. I.V IgG
Blocks Fc receptor system
2g/kg total,divided doses over 5days
High Dose Glucocorticoids with I.V IgG or antiRhoD theraphy.
Rituximab useful in Refractory ITP
Vaccinations-Pneumococcal,Meningococcal,H.influenzae must be given
TPO receptor antagonists
S/C and Oral preparation.
47. Heparin Induced Thrombocytopenia 1>Thrombocytopenia never very severe
2>not associated with bleeding but increase risk of thrombosis.
Antibody formation to complex of platelet specific protein platelet factor 4 and heparin.
Platelets exposed to heparin develop antibodies to heparin/Platelet factor 4 without consequences.
Fraction develop thrombocytopenia
Around 50% develop Heparin induced thrombocytopenia and thrombosis.
48. HIT develops after exposure to heparin for 5-10days.
It can occur before 5 days in those exposed to heparin in prior weeks/months(<100 days)
Delayed onset HIT can occur sometimes after several days of stopping heparin.
49. Diagnostic for HIT
Timing of platelet drop
Thrombosis and other sequelae
Other cause of thrombocytopenia not evident.
50. LAB testing HIT antibodies detected by 2 assays
1..ELISA with PF4/polyanion complex as antigen
2.Platelet Activation Assay
51. Thrombosis is a complication of HIT
Imaging studies should be done to rule it out
52. Treatment Switching over to another anticoagulant
Argatroban ,Lepirudin(Direct Thrombin Inhibitors) effective .
Direct Thrombin Inhibitor,bivalirudin and the antithrombin-binding pentasaccharide ,
Fondaparinux appear to be effective
Danaparoid, a mixture of glycosoaminoglycans with anti-Xa activity,effective
53. For patients with thrombosis,can be maintained with Warfarin for 3-6months
Introduction of warfarin alone in the setting of HIT or HITT may precipitate thrombosis, particularly venous gangrene, presumably due to clotting activation and severely reduced levels of proteins C and S.
Warfarin should only be started after alternative anticoagulation has been given for several days and the prothrombotic state has lessened.
54. Thrombotic Thrombocytopenic purpura Described in 1924 by Eli Moschcowitz
Characterised by pentad of findings
Microangiopathic hemolytic anemia
Renal function abnormalities
55. Pathogenesis Inherited (Upshaw-Schulman syndrome)
Normally the ultra-high molecular-weight multimers of von Willebrand factor (vWF) produced by the endothelial cells are processed into smaller multimers by a plasma metalloproteinases called ADAMTS13.
In TTP the activity of the protease is inhibited, and the ultra-high molecular-weight multimers of vWF initiate platelet aggregation and thrombosis
56. IDIOPATHIC TTP
More common in Women than men
HIV Infection and pregnant females.
Medication related TTP
secondary to antibody formation,(ticlopidine and possibly clopidogrel
direct endothelial toxicity(cyclosporine, mitomycin C, tacrolimus, quinine)
Withdrawal of agents might decrease the microangiopathy.
57. LAbs HCT Low Microangiopathic anemia
Peripheral Smear Schistocytes/polychromasia
Direct Coombs Negative
Indirect Bilirubin Elevated
58. Level of ADAMTS13 activity, as well as antibodies, can now be detectedvby laboratory assays.
However sensitivity and specificity not well known
59. Differentiation TTP&DIC TTP DIC Associated with
Isolated platelet consumption
No change in PT/PTT
No fibrinogen change
No D-dimer change Associated with
Coagulation cascade activation
Big change in PT/PTT
Reduction in fibrinogen
Elevation in D-dimer
60. treatment Plasma exchange
Can infuse Fresh Frozen Plasma if plasmapheresis not done
61. Hemolytic Uremic syndrome Acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia.
Children,episode of diarrhoea
Hemorrhagic in nature
Escherichia coli O157:H7 is the most frequent
Treatment is supportive
HUS not associated with diarrhoea has poor prognosis.
62. Pseudothrombocytopenia An in vitro artifact resulting from platelet agglutination via antibodies (usually IgG, but also IgM and IgA) when the calcium content is decreased by blood collection in ethylenediamine tetraacetic (EDTA) tubes.
If low platelet count is obtained,peripheral smear should help in distinguishing.
65. Normal Peripheral Blood Smear
66. Platelet Clumping Psuedothrombocytopenia
67. Abnormal Large Platelets
68. Schistocytes/decreased platelets Microangiopathic hemolytic anemia