Dr. SUNIL S VAIDYA ( MD DCH)

Dept of paediatrics

Ashwini Sahakari Rugnalay

Dr. MANDAR HAVAL (DCH DNB FELLOW IN NEONATOLOGY ).

THE BLEEDING CHILD

3 years old female child brought by Father

c/o- Bleeding from the nose and mouth since evening

• Patient was apparently alright and playful when mother noticed profuse bleeding from the nose and mouth.

• Bleeding was sudden in onset. It went on to continue for almost thirty min to one hour when father took her to ASR pediatric casualty

• No h/o fever with rash

• No h/o petechiae , purpura

• No h/o malena ,bleeding from other sites

• No h/o trauma , surgical procedure

• No h/o medications ( aspirin , warfarin, heparin)

• No h/o joint swelling , bone pain

• No h/o Haematuria

• No h/o Jaundice , Oedema

Past h/o similar episode of nasal bleeding 1 yr back. She had been investigated at that time. CBC

Hb- 7 g/dl , TLC 7900 cells/ cu mmplatelets 376000 ;clumps of platelets noted on ps

PT –INR NormalPTTK ProlongedBT Prolonged ,

Patient then received PCV, FFP,& Inj Vit K and discharged

Pt had 2nd episode 6month backShe received inj vitamin K , PCV and FFP transfusion at that time again and discharged.

And for 3rd episode she was referred to ASR Solapur.

No history of similar complaints in any of the family member of patient.

Child is born out of third degree

consanguinous marriage.

Registered pregnancy.

2 TT inj taken,received iron & folic acid.

No H/o HTN , DM , fever with rash .

No H/o medication

Full term ,2.6kg,Cried immediately after birth, born vaginally at Govt .Hospital

Uneventful Natal History. (No h/o cephalhematoma , jaundice , bleeding , No history of prolonged bleeding from umbilical stump)

Not much eventful.

No history of easy bruising or bluish discoloration on knees and elbow when baby started crawling

Completed up to date .

No h/o hematoma on the Site of injection given

All milestones achieved at appropriate age .

Father farmer by occupation , mother housewife.

According to modified kuppaswamy

classification upper middle class

Conscious , well oriented to person., time

Afebrile

HR 126/min

RR 26/min

BP 84 /56 mm of Hg in rt arm supine position

Pallor +No icterus , cyanosis , oedema , LNpathy .

Height 98 cm (85 %centile)

Weight 16 kg (>85 %centile)

Normal face, hair normal ,

Fontanel fused .

Eyes , ears Normal

Nose – Epistaxis + Throat -Normal

Bleeding from upper gums present.

No bleeding from other mucosal sites.

Neck Normal .

No petechiae , purpura , ecchymoses.

Spine , bone , joint normal , no tenderness or swelling.

CVS – S1S2 Heard Normal-No murmur.

RS – Air entry b/l equal.-Clear.

P/A – Soft-non tender-no hepato splenomegaly.

CNS – Tone , power ,reflexes - Normal

CBC – Hb - 9.8 g/dl- TLC - 8600 cells /cu mm - Platelet - 372000 / cu mm.

- Seen in clums on PS

PT- INR – 14.4 sec(Pt)-13.5 sec (Control)-Index- 93.75% -INR- 1.07 (N)

PTTK - 94.7 sec(Pt)- 32.2 sec(Control)

Bleeding time - > 10 min

PT is normal ( VII, X , II , V and fibrinogen)

APTT – INCREASED ( Factor XII, XI , IX, VIII, X , V, II and fibrinogen)

If there is unexplained prolongation of PT, PTT, or thrombin time, a mixing study is usually performed. Normal plasma is added to the patient’s plasma, and the PT or PTT is repeated. Correction of PT or PTT by 1 : 1 mixing with normal plasma suggests deficiency of a clotting factor, because a 50% level of individual clotting proteins is sufficient to produce normal PT or PTT. If the clotting time is not corrected or only partially corrected, an inhibitor is usually present.

PT – TEST - 10sec , CONT – 11sec

APTT – TEST – 72sec , CONT – 33sec

APTT correction studies –

½ test + ½ control – 34 sec

½ test + ½ aged serum – 83 sec (Factor 9)

½ test + ½ adsorbed plasma – 41 sec (Factor 8 )

Factor VIII Assay – 3.3 %(50 -150% U/ ml)

1) BLEEDING TIME –INCREASED with –Functional platelet

disorders- thrombocytopenias- vonWillebrand Disease

2) vWF acts as a chaperone for F VIIIso decreased levels of vWF leads to deficiency of Factor VIII

In vWD there are two conditions where factor VIII is LOW

1) vWD TYPE 2N

2)vWD TYPE 3

The distinguishing point in these two conditions

is vWF Ag Assay.

vWF antigen Assay – <1% (N 50 – 154 %)

Diagnosis???

von Willebrand diseaseType III

Most common inherited bleeding disorder

Autosomal inheritance

Due to either qauntitative or qualitative abnormality of vonWillebrand factor

1931 - Dr Erik von Willebrand first decribed this condition as hereditary pseudohaemophilia.

•1970- Discovery of facorproducing the disease described by vonWillebrandand was named after him.

•1980-vWF gene was cloned

Large multimeric glycoprotein

Synthesized in-Platelets (α granules)-Endothelial cells(Weibel palade bodies

Vascular injury

vWf adheres to subendothelial matrix

Conformational change in the vWF

Adhesion of the platelets to vWF through GlIb and activation of the platelets

Recruitment of additional platelets & exposing platelets to membrane phosphatidylserine which is important step for

Factor V & VIII bdependent steps in coagulation cascade

vWF also serves as the carrier protien for Factor VIII. A severe deficiency of vWF causes secondary deficiency of Factor VIII due to proteolytic degradaion of Factor VIII even though gene for Factor VIII is normal .

Clinical manifestions

- Excessive bruising

- Epistaxis

- Menorrhagia

- Procedures – Tonsillectomy- Tooth extraction etc.

Type I

• Most common (85%)

• Autosomaldominant

• Reduiced quantity of vWF but not absent

• Type 1c variant (accelerated clearance of vWF)

• Desmopressin is effective

Type II

• Qualitative abnormality of vWF

• Autosomaldominant

• Four subtypes

Type III(Most severe)

• Rare(I 1:5,00,00 0)

• Autosomal recessive

• Undetectable levels of the vWF &low levels of VIII

• MC presentationEpistaxisMenorrhagia

• Present in early age group

• Rarely can have IC/muscle/joint bleed likhaemophilia

• Desmopresin not effective

Type II A

• Lacks high or intermidiatevWF multimerdue to abnormal proteolysis or reduced secretion.

• Desmopressinnot much useful

• vWFreplacement therapy in significant bleeding

Type II B

• Mutation leading to hyperactive vWF

• Abnormal vWF bind spontaneously with platelets & rapidly cleared from circulation leading to thrombicytopenia.

• DesmopressinNEVER TO BE USED

Type II M

• Due to decresedplatelet binding function of vWF

• Levels of vWFactivity are significantly lower than vWF:Ag

• Desmopresinnot muschuseful even though release is normal due to absence of binding

Type II N

• Decreased binding of vWF to VIII but normal binding with platelets

• AKA-Autosomalhaemophilia

• Although desmopresinrelease abnvWF, sustained VIII levels may be occasionally inadequate for normal haemostasis

Monoclonal gammopathy: vWF neutralized by paraprotein (?)

Autoimmune disorders: Autoantibody to vWF Myeloproliferative disorder: large multimers absorbed

onto neoplastic cells (platelets?) Cardiovascular diseases (AS, VSD, etc): High shear

stress causes unfolding/proteolysis of large multimers Hypothyroidism: Decreased release of vWF from

endothelial cells

Treatment varies depending on cause/mechanism

DDAVP releases vWF from endothelial cells

Can be given IV or intranasally 0.3 mcg/kg IV, or 150 mcg per nostril

Typically causes 2-4 fold increase in blood levels of vWF (in type 1 vWD), with half-life of 8+ hours

Response to DDAVP varies considerably

Administration of a trial dose necessary to ensure a given patient responds adequately Peak response Duration of response

Sr.no Type Response

1 I Usually effective

2 II A Usually ineefective

3 II B May be contraindicated

4 II M Predicted to be effective

5 II N Rarely effective

6 III Ineffective

Type 2 or 3 vWD Active bleeding

Surgery or other invasive procedure

Type 1 vWD with inadequate response to DDAVP

THANK YOU !!!