By-Dr.Anupam

:

1. Overview of hemostasis

2. Clinical approach in making a diagnosis

3. LAB diagnosis

4. Review the most common bleeding conditions

Active process that clots blood in areas of blood vessel injury yet simultaneously limits the clot size only to the areas of injury.

HEMOSTASIS

Components:1. Vessel wall2. Platelets3. Coagulation proteins4. Anticoagulant proteins5. Fibrinolytics

Overview of Haemostasis

INJURY

Collagen Exposure

Platelet Adhesion and release

reaction

Platelet aggregation

VASOCONSTRICTION

Serotonin Platelet Phospolipid

Thromboxane A2

ADP

Primary haemostatic plug

Stable haemostatic plug

Tissue Factor

Coagulation

Thrombin

Fibrin

Fibrinolysis

CLOTTING FACTORS

Protein C/SFactor 8 & 5

Antithrombin3

PRACTICAL APPROACH TO A CHILD WITH BLEEDING HISTORY

HISTORYA.onset of symptomsB. Sites of bleedingC.Perinatal historyD.Gynecologic bleedingE. MedicationF. Diet

Family history

HISTORY

A)Onset-

• age

• acute vs chronic

• Timing of bleeding-immediate vs delayed

1. Mucocutaneous

a. Epistaxis

• Duration, frequency,

• Associated trauma (nose picking, allergy,infection)

b. Oral (bleeding after tooth brushing, after dental

extractions requiring sutures/packing)

c. Bruising (number, sites, size, raised [other than

extremities],

d. Gastrointestinal bleeding

SITES OF BLEEDING

2. Deepa. Musculoskeletal• Hemarthroses, unexplained arthropathy• Intramuscular hematomasb. Central nervous system hemorrhagec. Genitourinary tract3. Surgicala. Minor (sutures, lacerations, poor or delayed woundhealing)b. Major• Tonsillectomy and adenoidectomy• Abdominal surgery

Contd……

C. Perinatal historya. Superficial (bruising, petechiae)b. Deep• Circumcision• Central nervous system bleeding• Gastrointestinal bleeding• Cephalohematoma• Unexplained anemia or hyperbilirubinemia• Delayed cord separation, bleeding after cordseparationc. Vitamin K administrationd. Maternal drugs

D.MEDICATIONSa. Aspirin and NSAIDSb. Anticoagulantsc. Antibioticsd. AnticonvulsantsE. Dieta. Vitamin Kb. Vitamin C

II. Family History.

PHYSICAL EXAMINATION-

• Healthy and sick looking• Vitals signs and growth parameters• Joint examination for :

A)chronic arthropathyB)joint laxity

• Extremities examination fot thumb or radial anomalies(TAR)

• Lymphadenopathy/hepatosplenomegaly

Contd………Skin examination-• pallor,• hematoma,• petechiae,• ecchymosis,• telangiectasias,• poor wound healing,lax skin

Hemarthrosis

PETECHIAEECCHYMOSIS,

Approach to a bleeding patient

LABORATORY WORK UP-

1) C.B.C./PLATELET COUNT2) PERIPHERAL SMEAR- MORPHOLOGY3) P.T. [Prothrombin time]4) a.P.T.T. [ Activated partial thromboplastin

time]

Control bleeding; give fluids arrange blood;order

CBC,PT,aPTT stat

Normal PT,aPTT and decreased platelet

Normal morphology and size of platelets

Perform bone marrow examination

Normal megakaryocytes Decreased megakaryocytes

Peripheral platelet destruction

1. ITP

2. Alloimmune thrombocytopenia

3. Drug induced throbocytopenia

4. TTP

5. HELLP

6. Splenic sequestration

7. Others(sepsis,malignancy)

Decreased production

1. Heriditary thrombocytopenia

2. Fanconi anemia

3. Myelopthisic disorders

4. Drug induced aplasia

5. Viral aplasia

6. Acquired megakaryocytic purpura

Control bleeding; give fluids arrange blood;order

CBC,PT,aPTT stat

Prolonged PT,aPTT and decreased

platelet

Prolonged PT and /or aPTT

Normal platelets

Sick child Healthy child

Investigate for liver disease

1. Acute viral hepatitis

2. Drug induced hepatitis

3. Autoimmune hepatitis

4. Hepatotoxic agent

ingestion

Both PT and

aPTT prolonged

PT normal and

PTT prolonged

VIT K def

• Give vit k

• probiotics

Clotting factor

def

Hemophilia

A

B

C

Control bleeding; give fluids arrange blood;order

CBC,PT,aPTT stat

Healthy child Sick child

Bleeding due to

local factors like

trauma,

anatomic

abnormalities

Qualitative platelet defects

1. Order platelet

aggregation studies

2. Order platelet surface

GP analysis

Compromised vascular

integrity

1. Sepsis

2. Hypoxia

3. Acidosis

4. prematurity

Normal PT and APTT and normal platelet counts

PT PTT FIBRINO-GEN

PLATELETS FDPs Clinical keys

DIC ↑ ↑ ↓ ↓ ↑ Shock

Liver failure↑ ↑ ↓ N/↓ N Jaundice

Vitamin K def ↑ ↑ N N N Malabsorpt

ion

Sepsis without shock

↑ ↑ N N ↑/N Fever

DD’s for DIC

Some common bleeding conditions

Causesa) Infectious-CMV,HCV,HIV

b) Vaccination

c) SLE

d) APLA synd

e) Drugs-quinidine,sulfonamide,heparin

f) CVID

g) Lymphoproliferative disorder

Newly diagnosed ITP-diagnosis to 3months

Persistent ITP-3to 12months of diagnosis

Chronic ITP->12months

Corticosteroid dependence ITP-need for ongoing or repeated administration of steroid to maintain platelet count in excess of 30x109

or avoid bleeding.

Severe ITP-bleeding at presentation of sufficient magnitude requiring treatment or occurrence of new bleeding symptoms requiring intervention

RefractoryITP-presence of severe ITP occuringafter splenectomy

MANAGEMENT

GRADE 1 MINOR BLEEDINGFEW PETECHIAE(<100)<5 SMALL MUCOSAL BLEED

Observation

GRADE 2 MILD BLEEDING>100 PETECHIAE>5LARGE BRUISE(>3cm)NO MUCOSAL BLEEDS

ObservationTreatment in selected childred

GRADE 3 MODERATE BLEEDINGOVERT MUCOSAL BLEEDMENORRHAGIA

Intervention to reach grade1 or gr2 in selected children

GRADE 4 MUCOSAL BLEEDS OR SUSPECTED INTERNAL BLEEDS

INTERVENTION

DRUGS APPROX RESPONSE

RESPONSETIME

TOXICITY

Iv anti D 50-75mcg/kg

50-77% Within24hrs

Headache,fever

IVIG0.8-1g/kg SD

>80% 1-2days Fever

Prednisolone1-2mg/kg-14d or4mg/kg 4days

¾ patient responddepending on dose

2-7days Gastritis

Wait & watch

2/3 ptimprove spontaneouslywithin 6months

Days to month

-

a)Children and adolscents

PLTs <50,000/dl and bleeding

PLTs<50,000/dl and invasive procedure

PLTs <20,000/dl and marrow failure and hemorragic factors

PLTs any counts,but with PLTs dysfunction plus bleeding or on an invasive procedure

Infants within the first 4 months of life:

PLTs <1lakh/dl and bleeding

PLTs<50,000/and an invasive procedure

PLTs<1lakh/dl and clinically unstable

PLTs any counts,but with PLTs dysfunction plus bleeding or on an invasive procedure

Caused by an absence or decreased amount of a procoagulant –

1. VIII -Hemophilia A affects ~ 1:5000 males2. IX -Hemophilia B affects ~ 1:30000 males3. XI –Hemophilia C – Rare /Ethnicity

• Hallmark –HEMARTHROSIS• Easy bruising ,intramuscular

hematomas,heamarthrosis• Life threatening condition like bleed into

iliopsoas muscle,GI bleed

Prolonged PTT(reduced level of 8 & 9)

Other screening test of hemostatic mechanism(platelet,bleeding time,PT)are normal.

Specific assay for factors VIII & IX confirms the diagnosis

Dose calculation of r factor 8 and factor 9

Dose of factor 8

=%desired(rise in f8)xbody weight(kg)x0.5

Dose of factor 9

=%desired(rise in f9)xbody weight(kg)x1.4

Factor 8 concentrates-

A)Plasma -derived factor VIII as well as factor VIII/von Willebrand factor (vWf) concentrates are prepared from cyroprecipitates and contain vWf and moderately enriched factorVIII.

B) Recombinant factor -concentrates are prepared in animal cell cultures using biotechnological procedures

Package Sizes-250/500/1000/1,500/2,000 U/package.

storage temperature for concentrates is 2–8 °C

Diluent-sterile waterLyophilised powderRoute-IV

baxject

-DDAVP’s

VWF tethers platelet to injured endothelium

VWF serves as carrier protein for factor 8

Stored in WEIBEL PALADE BODIES in endothelial cells

Facilitates its ability to bind to platelets by GP1b receptor.

Easy bruisability

Epistaxis or gingival bleeding

Menorrhagia

Post-surgical bleeding

Bleeding post-dental extraction

Sub types of VW

Type 1 Partial quantitative deficiency of vWF

Type 2 Qualitative variants of vWF

A - Absence of HMW vWF multimersB - Same as 2A and increased affinity for platelet gp IbM - Abnormal function not caused by absence of HMW N - Decreased affinity for factor VIII

Type 3 Complete deficiencey of vWF & Behave as Severe Hemophilia A

VWf concentrates-

Desmopressin sprays

antifibrinolytics

VWD treatment

factor XIII is responsible for the crosslinking of fibrin to stabilize the fibrin clot,

symptoms -delayed hemorrhage

Typically, patients have trauma 1 day and then have a bruise or hematoma the next day.

C/f

mild bruising, delayed separation of the umbilical stump beyond 4 wk in neonates,

poor wound healing,

screening tests –for hemostasis are normal

The normal clot remains insoluble in the presence of 5M urea, whereas in a patient with XIII deficiency, the clot dissolves.

The half-life of factor XIII is 5-7 days

There is a heat-treated, lyophilized concentrate of coagulation factor XIII available to treat bleeding episodes or for prophylaxis.

Blood products

• Indication1)to increase oxygen delivery in an anemic patient2)acute blood loss greater than 25-40% in blood volume.

Dose-10ml/kg of RBC will increase Hb by 2.5-3g/dl

Recommneded temp-33-35 C

Can be single or pooled whole blood

1U/10 kg=increase upto 50,000

Stored in mechanical agitator at 22 C upto5days

Freezing plasma at -18 C within 8hrs of separation from whole blood

Contains all coagulation factors

Stored at -18C for 1yr

Prior to administration—thawed at 36-38C

10-15ml/kg over 30-120mins

Contains fibrinogen(150mg/bag),

factor 8(80u/bag),VWf,factor 13

Highly concentrated form of plasma protein that settle down at bottom as ppte when frozen plasma is slowly thawed at 1-6 C

Dose-10-20 ml/kg

Thank you