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Bleeding disorder
1. Approach to a bleeding disorder,
Approach to thrombocytopenia,
Idiopathic thrombocytopenia (ITP)
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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6. COAGULATION PHASE
THROUGH TWO SEPARATE
PATHWAYS THERE IS
CONVERSION OF FIBRINOGEN
TO FIBRIN
7. FIBRINOLYTIC PHASE
ANTICLOTTING MECHANISMS ARE
ACTIVATED TO ALLOW CLOT
DISINTEGRATION AND REPAIR OF
THE DAMAGED VESSEL
8. HEMOSTASIS
DEPENDENT UPON:
Vessel Wall Integrity
Adequate Numbers of Platelets
Proper Functioning Platelets
Adequate Levels of Clotting Factors
Proper Function of Fibrinolytic
Pathway
9. Coagulation cascade
Intrinsic system (surface contact) Extrinsic system (tissue damage)
XII XIIa Tissue factor
XI XIa
IX IXa VIIa VII
VIII VIIIa
X Xa
V Va
II IIa (Thrombin)
Fibrinogen Fibrin
Vitamin K dependant factors
10. LABORATORY EVALUATION
• Platelet Count
• Bleeding Time (BT)
• Prothrombin Time (PT)
• Partial Thromboplastin Time (PTT)
• Thrombin Time (TT)
11. Laboratory Evaluation of the
Coagulation Pathways
Partial thromboplastin time(PTT) Prothrombin time(PT)
Intrinsic pathway Extrinsic pathway
Thrombin time Common pathway
Fibrin clot
12. Laboratory Evaluation of the
Coagulation Pathways
• PT prolonged in extrinsic and common
pathway
• APTT prolonged in intrinsic and common
pathway
• PT &APTT – prolonged in common pathway
,liver dysfunction ,DIC
• DIC – thrombin time is also prolonged
• Factor XIII deficiency – platelet ,APTT,PT,BT-
Normal
13. Diagnostic Approach
• Increased BT –
a) Platelet decreased – ITP
b) Platelet normal – anaphylactoid purpura
• Increased CT –
a) only PT prolonged – Factor VII deficiency
b) only APTT prolonged – factor – VIII,IX,XI,XII
and von willebrand’s disease
14. Diagnostic Approach
c) Both PT & APTT prolonged –vit –k deficiency,
severe liver ds, cong deficiency of factor V,
X.fibrinogen deficiency ,DIC
28. IDIOPATHIC / IMMUNE
THROMBOCYTOPENIC PURPURA
DEFINITION : is characterised by
-Thrmbocytopenia < 100.000/cm
- Shortened PLT. survival
-Presence of antiplatelet AB in the plasma.
-Increased Megakaryocytes in BM
29. BACKGROUND
Most common causes of symptomatic
thrombocytopenia in children.
Incidence - 3 and 8 cases per 100,000
children/yr
Before a diagnosis of ITP – R/O other
common causes of thrombocytopenia
(concurrent infection , autoimmune disorders ,
malignancy , bone marrow failure .. )
30. CLASSIFICATION
1.Acute ITP (children)- PLT returns to normal
value before 6mth.
2.Chronic ITP (adults) - PLT remains low
after 6mth also
3.Secondary ITP (follow other diseases
4.RECCURRENT:-PLT count decreases after
becoming normal
31. ETIOLOGY
Usually benign transient immune-mediated
thrombocytolytic condition
Autoantibodies (usually IgG) directed against platelet
membrane antigens (especially glycoprotein complex
IIb/IIIa) are present
Thrombocytopenia results from phagocytosis of
antibody-coated platelets by the reticuloendothelial
system
34. CLINICAL PRESENTATION
2- 10 years (peak 2 to 5 years )
Patients < 2 years or > 10 years at
presentation are atypical
No seasonal variation
History of a preceding infection (1-4 wks
back), in 50 to 85 % of pediatric cases
Post-vaccination cases also have been
reported ( MMR )
35. CLINICAL PRESENTATION
• Previously healthy child - sudden Skin and mucous
membrane bleeds - Petechiae, purpura
ecchymosed, Gingival bleeding and epistaxis ,
gastrointestinal , genitourinary
Conjunctival and retinal hemorrhages may
occur
Life-threatening bleeding, (ICH), - is very rare,
occurring with an incidence of 0.1 to 1.0 %
37. CLINICAL PRESENTATION
No other systemic symptoms - fever, anorexia,
weight loss, or bone or joint pain
No significant enlargement of lymph nodes,
liver, or spleen is present
38. LABORATORY STUDIES
For the typical case of ITP :
CBC
platelet count
peripheral blood smear (often large
platelet forms are seen )
Mean Platelet Volume increased
Bleeding time prolonged
PT/ APTT normal
Platelet antibodies in 70-90 %
40. LABORATORY STUDIES
For the atypical case of ITP :
viral antibody titers (including HIV)
Coombs' test
Reticulocyte count
Studies for collagen vascular :
ANA , Anti dsDNA, ANCA etc
Studies for rheumatoid disorders:
RF
42. LABORATORY STUDIES
BONE MARROW EXAMINATION (BME)
In the past, BME was performed routinely in
children with suspected ITP
BME are unnecessary in the "typical" case of
childhood ITP
Bone marrow aspiration and biopsy is reserved
for - atypical presentation
BME - who initially was diagnosed as ITP but
subsequent clinical course is inconsistent with
the natural history of acute ITP
43. DIFFERENTIAL DIAGNOSIS
1. Aplastic anemia
2. Leukemia ( ALL )
3. Autoimmune disease (SLE)
4. HSP
5. Infection - hepatitis, HIV
6. Drug exposure - heparin, quinidine,
sulfonamides
44. MANAGEMENT
80 to 90 % of cases recover spontaneously within a few
months (3-6 months) even without treatment
Restriction of activity and avoidance of medications with
antiplatelet activity (aspirin , ibuprofen ,NSAID)
Guidelines suggest :
Platelet counts >30,000 no symptoms – no
treatment
Platelet counts <30,000 with symptoms –
treatment
46. CORTICOSTEROIDS
Steroids reduce the risk of symptoms by -
1. Improving vascular integrity
2. Diminishing antibody affinity for the
platelet membrane
3. Reducing antibody production
4. Reducing reticuloendothelial system
phagocytosis of antibody-coated
platelets
47. Dosage regimens
Prednisone 1-4 mg/kg per day for 2 to 4
weeks
Pulse IV methylprednisolone as high as 50
mg/kg per day for 3 to 7 days
Occasionally, a second course of
treatment may be necessary if significant
hemorrhagic symptoms again develop
48. CORTICOSTEROIDS
Chronic administration of steroids -
Avoided
Alternative therapies - IVIG or Anti-D
should be considered who need
prolonged or repeated corticosteroid
therapy
49. IVIG
MoA: interferes with macrophage Fc receptor
clearance
Rapid improvement in platelet numbers - 95%
patients within 48 hrs
Dose - 400 mg/kg per day for five days
- 1 gm/kg for one to two days
The higher, shorter dosage schedules appear to
be preferable
50. IVIG
The side effects include :
1. Nausea and vomiting (63 %)
2. Headache (56 %)
3. Fever (19 %)
4. Neutropenia (absolute neutrophil count
<1500/microL) 30 %
Cost must be considered in the selection of
therapy for ITP
51. ANTI-D IMMUNE GLOBULIN (Anti-Rho(D)
MoA: anti-D results in blockade of Fc receptors by
antibody coated RBCs in place of antibody coated
platelets
Dose - single dose of 50 µg/kg
80-85 % patients show rise in platelets within 48 hrs
Given to children with a Hb > 10 g/dl
One to two weeks after administration, a fall in the Hb
level of 1 to 1.5 grams - as a result of mild hemolysis of
the patient's Rho(D)-positive red cells
52. OUTCOME
80 % -90% - recovers spontaneously within three
months of presentation, with or without therapy
10 % recovers in the next few months
15 to 20 % - have moderate or major hemorrhage
0.1 to 1 % - Life-threatening bleeding(ICH) is rare
<5 % with acute ITP have recurrent acute
thrombocytopenia
53. CHRONIC ITP
Definition - persistence of thrombocytopenia
beyond six months from the time of diagnosis
10 % of patients with typical ITP will have
chronic ITP
Patients who have atypical features at
presentation are more likely to have chronic
disease
54. CHRONIC ITP ( Management )
Aim of treatment - should focus on minimizing
the risk for bleeding
Many patients will require no treatment
Even after years, a significant proportion of
such patients will improve
55. CHRONIC ITP ( Management )
Corticosteroids :
Periodic short courses or pulses of corticosteroids
For steroid dependent patients - alternate day dosing
may be effective in preventing bleeding while
reducing side effects
56. CHRONIC ITP ( Management )
Immunoglobulin therapy :
IVIG or anti-Rho(D)- effective in chronic ITP who
are resistant to steroids
All of these strategies offer temporary relief of
symptoms and improvement in platelet numbers
Very costly
57. CHRONIC ITP ( Management )
Splenectomy :
Effective in 60 to 90 % of children with chronic ITP
Overwhelming post-splenectomy infection
Presplenectomy immunizations and subsequent
penicillin prophylaxis are necessary for all age groups
58. CHRONIC ITP ( Management )
Splenectomy :
No universally accepted standards for the timing
of splenectomy in chronic ITP
Guidelines recommend waiting until at least 12
months after diagnosis
8)Immunosupressive agents - Cyclophoshamide
61. Neonatal thrombocytopenia
Due to transfer of maternal antibodies directed
against fetal platelets
1. Neonatal alloimmune TP-(NATP) –
development of maternal antibody against
antigens present on fetal platelets
- develops symptoms in first few days of life
- No maternal thrombocytopenia
64. Platelet transfusions
• Source
– Platelet concentrate (Random donor)
Each donor unit should increase platelet count
~10,000 /µl
– Pheresis platelets (Single donor)
• Storage
– Up to 5 days at room temperature
• “Platelet trigger”
– Bone marrow suppressed patient (>10-20,000/µl)
– Bleeding/surgical patient (>50,000/µl)
65. Danzol 400 mg/m2/d for 3 mth.
9)PLASMAPHERESIS
10) T/T Of life threatening ITP:-
PLT. TRANSFUSION
SOLUMEDROL 500 Mg/m2/day IV TID.
IVIG 2g/kg
emergency Splenectomy.
Vincristine 2 mg/kg IV.
PROGNOSIS;-
EXCELENT 70-80 % recover ithin 6mth.
spontaneous remission in 1 yr- 5yrs.
66. Approach to the thrombocytopenic
patient
• History
– Is the patient bleeding?
– Are there symptoms of a secondary illness? (neoplasm,
infection, autoimmune disease)
– Is there a history of medications, alcohol use, or recent
transfusion?
– Are there risk factors for HIV infection?
– Is there a family history of thrombocytopenia?
– Do the sites of bleeding suggest a platelet defect?
• Assess the number and function of platelets
– CBC with peripheral smear
– Platelet function study
68. Platelet transfusions - complications
• Transfusion reactions
– Higher incidence than in RBC transfusions
– Related to length of storage/leukocytes/RBC mismatch
– Bacterial contamination
• Platelet transfusion refractoriness
– Alloimmune destruction of platelets (HLA antigens)
– Non-immune refractoriness
• Microangiopathic hemolytic anemia
• Coagulopathy
• Splenic sequestration
• Fever and infection
• Medications (Amphotericin, vancomycin, ATG, Interferons)
69. Approach to the WERLHOF’S DISEASE
• History
– Is the patient bleeding?
– Are there symptoms of a secondary illness? (neoplasm,
infection, autoimmune disease)
– Is there a history of medications, alcohol use, or recent
transfusion?
– Are there risk factors for HIV infection?
– Is there a family history of thrombocytopenia?
– Do the sites of bleeding suggest a platelet defect?
• Assess the number and function of platelets
– CBC with peripheral smear
– Bleeding time or platelet aggregation study
– TORNIQUET / RUMPEL-LEEDE TEST:-
71. DIAGNOSIS :-
TPC ,Hb % , Haptoglobin , hemoglobinuria
Decreased plasma factor - VIII & vWF.
GINGIVAL BIOPSY = Presense of segmantal hyaline microthrombi in
the microvasculature.
TREATMENT : -
PLASMAPHERESIS
FFP
STEROIDS
ANTIPLATELETS AGENTS.
SPLENECTOMY.
72. NONTHROMBOCYTOPENIC PURPURA
1)ANAPHYLACTOID PURPURA
2)INFECTIONS (Meningococcus, measles, rubella, SBE)
3)DRUGS(SULFA)
4)PURPURA FACTITIA:-It is a self inflictted lesions in a linear fashion commonly over accessible
parts of body due to Psychopathic disorder.
74. ESSENTIAL THROMBOCYTHEMIA
Diagnosed by :-TPC > 6000.000/cmm, Hb% <13gm%
RCM < 36ML/KG.
NORMAL IRON IN BM.
ABNORMAL PLT FUNCTION TEST.
NO KNOWN CAUSE OF THROMBOCTYTOSIS
- ve philadelphia chromosome.
-ve BM fibrosis.
Thrombotic & haemorrhagic features common.
TREATMENT:- Anti-platelet agents = ASA, Dipyridamole(3-6 mg/kg/d
PLT lowering drugs = Hydroxyurea - 20-30mg/kg od
Alpha 2- interferon.
75. Thank you
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Medical Post [ www.themedicalpost.net ]