A Case of Bleeding disorder PROFESSOR AND HEAD OF THE DEPARTMENT DR.V.T. PREMKUMAR MD ASSISTANT PROFESSORS DR. PEER MOHAMMED MD DR. MURUGESAN MD DR. MURALIDHARAN MD DR. SIVARAMASUBRAMANIAM MD

Clinical presentation 21 year old female came with m ajor complaints of Easy bruisability since 6 years of age Bleeding gums since 8 years of age Excessive menstruation since 13 years of age HOPI : Patient was apparently normal before 6 years of age Easy bruisability Developed at 6 years of age No history of joint hyperextensiblity Epistaxis Developed at 8 years of age No history of excessive bleeding during tooth eruption No h/o excessive bleeding during tooth eruption No h/o No h/o bleeding piles No h/o hemetemesis, hemoptysis No h/o fever with chills h/o easy bruisability h/o frequent blood tranfusions (yearly around 2-3 times) h/o easy fatiguability + h/o previous similar episodes + h/o seizures + (GTCS)

Excessive menstruation Since 13 years of age lasting for 8 – 12 days Passage of clots Changes pads more than 6 times per day Requires multiple admissions and blood transfusions Easy fatiguablity for past two years Palpitations and chest pain On unaccustomed work Releived by rest

No h/o epistaxis No h/o Joint bleed, pain or swelling No h/o Haematuria No h/o Haematemesis No h/o Fever with chills and rigor No h/o Drug intake No h/o Jaundice,itching, abdominal distension,leg swelling No h/o Reduced urine output, facial puffiness. No h/o Constipation, cold intolerance, hoarsness of voice.

Past history: No H/o Tuberculosis, Diabetes,Hypertension, Seizure disorder No H/o Hypothyroidism, Liver disease, Renal disease, No H/o Immunodeficiency states, Bronchial asthma. No H/o Steroid or NSAID abuse. No H/o Previous surgeries Family history: H/o Similar bleeding manifestations in her elder brother. He died due to an unknown cause at the age of 8 years. History of a still birth before the birth of this girl. Her eldest sister is healthy and has no specific complaints at present. No history of bleeding disorder in parents.

Pedigree chart Still birth Died at 8 years

Clinical Examination GENERAL EXAMINATION : Patient well built and nourished Conscious, oriented Afebrile – Pallor ++ – Not icteric – No clubbing – No cyanosis – No pedal oedema – No lymphadenopathy – Multiple briuses + on the shin – Multiple petechiae in the oral mucosa +

Vitals Blood pressure : 100/70 mm Hg (R upper limb in sitting posture) 90/70 mm Hg in standing posture Pulse : 85/min regular, normal volume, no specific character, palpable in all accesible peripheral vessels, no radioradial /femoral delay Temperature : 98.7 degree F JVP not elevated Saturation : 98 % in room air

Systemic examination CVS : S1 S2 heard systolic murmur over precodium RS : bilateral air entry + no added sounds P/A : soft, not tender no organomegaly or free fluid CNS : no focal neurological deficit

Hb 7.4 gm% TC 10,700 CELLS/mm3 DC P75% L 17% M 7% ESR 59 MM/hr PLATELETS lakhs /mm3 PCV 25 % LFT SGOT/PT 35/24 SERUM PROTEINS 7.2 A/G – 4.7/2.5 SERUM ELECTROLYTES NA – 134 mEq/L K-4.1 mEq /L Cl – 101 mEq/L RBS – 122 mg/dl RFT – 19 / 0.7 Routine investigations ECG – Within normal limits USG – normal study CXR – no abnormalities

Screening Tests for Haemostasis 1.Bleeding time > 15 minutes 2.Platelet count 2.27 lakhs 3.Mean platelet volume 7.1 fl 4.Peripheral smear microcytic hypochromic anemia. Platelets normal in count and morphology 5. Prothrombin time 10.3 secs [ Normal : ] 6. Activated partial thromboplastin time 68.7 secs [ Normal : 25 – 38.4]

Platelet Specific tests Aggregation -- Defective with ristocetin but corrected with addition of cryo precipitate

Clotting factor specific tests FACTOR BASED TESTS PATIENT VALUE REFERENCE VALUE PROTHROMBIN TIME 10.3 seconds 10 – 12.5 seconds ACTIVATED PARTIAL THROMBOPLASTIN TIME 68.7 seconds 25 – 38.4 seconds aPTT with Control plasma 34.2 seconds 25 – 38.4 seconds aPTT with Factor VIII deficient plasma 64 seconds 25 – 38.4 seconds aPTT with Factor IX deficient plasma 30.0 seconds 25 – 38.4 seconds

Specific factor assays TestsPatient value Reference value Factor VIII assay1.5 %50 – 150 % VWF Rco Value 8.0% % VWF Ag 0 IU / dl Fibrinogen329 mg /dl mg/dl

Clinical pointers for a platelet defect in this patient Absence of haemarthrosis menorrhagia Bleeding gums and epistaxis After ruling out all systemic causes of bleeding diathesis

Laboratory evidence for disease diagnosis Suggestive of Von Willebrands Disease Type 3 Absent VW FACTOR Reduced Factor VIII Elevated aPTT corrected with Factor VIII Normal platelets,

Final diagnosis VON WILLEBRANDS DISEASE TYPE 3

Treatment Blood transfusion Cryoprecipitate transfusion T. Medroxy progesterone Acetate 10mg TDS T. B Complex T. Ferrous Sulphate T. Vit C

Another case of bleeding disorder evaluated 24 year old female Mrs. Aruna kumari Diagnosed to have bleeding disorder since 8 months of age. Provisionally diagnosed as a case of Bernard Soulier syndrome. Multiple hospital admissions since then for epistaxis, easy bruisablity and menorrhagia. The patient presented to GRH madurai with significant menorrhagia necessitating blood transfusion and hormonal contraceptives for arresting menorrhagia Examination and routine investigations were normal

Bleeding profile 1.Bleeding time > 15 minutes 2.Platelet count 1.27 lakhs 3.Mean platelet volume 6.3 fl 4.Peripheral smear Platelets normal in count and morphology 5. Pro thrombin time 10.3 secs [ Normal : ] 6. Activated partial thromboplastin time 35.3 secs [ Normal : 25 – 38.4] 7. Aggregation Aggregation followed by disaggregation with ristocetin Absent response to collagen, ADP and Epinephrine

100% of the platelets shows absent expression for GP IIb IIIa against CD42b Tests Patient value Reference value Factor VIII assay299 %50 – 150 % VWF Rco Value98.7 % % Fibrinogen289 mg /dl mg/dl

Revision of Diagnosis after ruling out other systemic diseases Suggestive of Glanzmanns thrombasthenia Absent expression of GP IIb IIIa against CD 42 b Normal platelets,PT, aPTT, Factor VIII Ristocetin aggregation pattern and absent response to ADP,Epinephrine Absence of haemarthrosis menorrhagia Bleeding gums and epistaxis

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