APPROACH TO A APPROACH TO A BLEEDING CHILDBLEEDING CHILD

PRIMARY HEMOSTASISPRIMARY HEMOSTASIS1.1. Platelet formation at site of injuryPlatelet formation at site of injury2.2. Occurs within seconds of injuryOccurs within seconds of injury3.3. Important in stopping blood loss from Important in stopping blood loss from

capillaries,small arterioles and venulescapillaries,small arterioles and venules

SECONDARY HEMOSTASISSECONDARY HEMOSTASIS1.1. Results in fibrin formationResults in fibrin formation2.2. requires several miniutesrequires several miniutes3.3. Important in large vesselsImportant in large vessels4.4. Prevents recurrent bleeding frm occuring hrs Prevents recurrent bleeding frm occuring hrs

or days after injuryor days after injury

PRIMARY HEMOSTASISPRIMARY HEMOSTASIS

SECONDARY HEMOSTASISSECONDARY HEMOSTASIS

CLINICAL EVALUATIONCLINICAL EVALUATION

LOCAL OR SYSTEMICLOCAL OR SYSTEMIC L0CAL ~single site,reccurs from the same site.L0CAL ~single site,reccurs from the same site. SYSTEMIC~excessive bleeding,eg:after tooth SYSTEMIC~excessive bleeding,eg:after tooth

extraction,bleeding is greater then expected for the site extraction,bleeding is greater then expected for the site of injury.of injury.

INHERITED OR AQUIREDINHERITED OR AQUIRED

INHERITED~presents in infancy and childhoodINHERITED~presents in infancy and childhood Bleeding from umbalical cordBleeding from umbalical cord Cephalohaematoma without difficult labourCephalohaematoma without difficult labour Bleeding after tooth extractionBleeding after tooth extraction Family historyFamily history HaemarthrosisHaemarthrosis

SEX LINKEDSEX LINKEDX linked recessiveX linked recessive

Factor VII ~hemophilia AFactor VII ~hemophilia AFactor IX ~hemophilia BFactor IX ~hemophilia BWiscott aldrich’s syndromeWiscott aldrich’s syndrome AUTOSOMAL RECESSIVE DISORDERAUTOSOMAL RECESSIVE DISORDERh/o consangunityh/o consangunitySeen in factor II,V,VII,X,XI,XII,XIII,prekalliekrien and high Seen in factor II,V,VII,X,XI,XII,XIII,prekalliekrien and high

molecular weight kininogen.molecular weight kininogen. AUTOSOMAL DOMINANT PATTERNAUTOSOMAL DOMINANT PATTERNVariable penetrance and expressivityVariable penetrance and expressivityMany members of the family may be affectedMany members of the family may be affected

ex :von willebrand’s diseaseex :von willebrand’s disease Some types of qualitaSome types of qualita tive platelet defectstive platelet defects DysfibrinogenemiaDysfibrinogenemia Heriditary hemorrhagic telangectasiaHeriditary hemorrhagic telangectasia

Negative family history does not rule out inherited bleeding disorder.Negative family history does not rule out inherited bleeding disorder. ACQUIRED DISORDERACQUIRED DISORDER Presents later in lifePresents later in life Negative family historyNegative family history h/o ingestion of drugs..asirinh/o ingestion of drugs..asirin Underlying systemic disorderUnderlying systemic disorderLiver disease with factor deficiencyLiver disease with factor deficiencyMalabsorbtion statesMalabsorbtion statesPromyelocytic leukemiaPromyelocytic leukemiaMyeloproliferative disorderMyeloproliferative disorderAmyloidosis~factor x deficiency,capillary fragility,,SLE:,factor Amyloidosis~factor x deficiency,capillary fragility,,SLE:,factor

defeciency,thrombocytopeniadefeciency,thrombocytopenia,,

SYNDROMES KNOWN TO BE ASSOCIATED WITH SYNDROMES KNOWN TO BE ASSOCIATED WITH BLEEDING DISORDERBLEEDING DISORDER

1.1. Heriditary hemorrhagic telangectasiaHeriditary hemorrhagic telangectasia2.2. Afibrinogenemia,factor XIII def….keloidsAfibrinogenemia,factor XIII def….keloids3. Ehler danlos,cigarette paper scar,hyper extensible 3. Ehler danlos,cigarette paper scar,hyper extensible

joints.joints.4. Factor V :syndactaly,history of bleeding 4. Factor V :syndactaly,history of bleeding 5. Wiscott aldrich 5. Wiscott aldrich

syndrome:thrombocytopenia,eczema,otitis syndrome:thrombocytopenia,eczema,otitis media,recurrent infectionmedia,recurrent infection

6. albinism…functional defect of platelets6. albinism…functional defect of platelets7.Thrombocytopenia absent radius7.Thrombocytopenia absent radius8. Kasalbach merrit: giant hemangioma,thrombocytopenia8. Kasalbach merrit: giant hemangioma,thrombocytopenia

m

MANIFESTATIONSMANIFESTATIONS DEFECTS OF DEFECTS OF PRIMARY PRIMARY HEMOSTASISHEMOSTASIS

DEFECTS OF DEFECTS OF SECONDARY SECONDARY HEMOSTASISHEMOSTASIS

ONSET OF BLEEDINGONSET OF BLEEDING IMMEDIATEIMMEDIATE DELAYEDDELAYED

SITE OF BLEEDSITE OF BLEED SUPERFICIALSUPERFICIAL DEEPDEEP

PYSICAL FINDINGSPYSICAL FINDINGS PETECHIAE PETECHIAE ECCHYMOSIECCHYMOSISS

HEMATOMA HEMATOMA HEMARTHROSIHEMARTHROSI

REPONSE TO THERAPYREPONSE TO THERAPY IMMEDIATEIMMEDIATE SUSTAINED SUSTAINED SYSTEMIC THERSYSTEMIC THER

LABORATORY EVALUATIONLABORATORY EVALUATION

SCREENING TESTSSCREENING TESTS1.1. Complete blood countComplete blood count2.2. Peripheral blood smearPeripheral blood smear3.3. Platelet countPlatelet count4.4. PT,APTT,TTPT,APTT,TT5.5. BT,CT,clot retraction timeBT,CT,clot retraction timeSPECIAL CONFIRMATORY TESTSPECIAL CONFIRMATORY TEST1.1. Factor assayFactor assay2.2. Correction studyCorrection study3.3. Platelet function disorderPlatelet function disorder

CBC & PBSCBC & PBS

1.1. Extent of AnaemiaExtent of Anaemia2.2. Involvement of other cell linesInvolvement of other cell lines3.3. Extent of thrombocytopeniaExtent of thrombocytopenia Clumps of platelets rules out deficiencyClumps of platelets rules out deficiency Absence – Severe thrombocytopeniaAbsence – Severe thrombocytopenia Platelets not in clumps – Functional Platelets not in clumps – Functional

disorderdisorder Large platelets – Bernard Soulier syndromeLarge platelets – Bernard Soulier syndrome Large, young platelets – Regenerative Large, young platelets – Regenerative

thrombocytopeniathrombocytopenia

PLATELET COUNT PLATELET COUNT Particle cell counter, using phase contrast microscopeParticle cell counter, using phase contrast microscope PLATELET FUNCTION ANALYSERPLATELET FUNCTION ANALYSER Early stage platelet function and VWF interactionEarly stage platelet function and VWF interaction PFA – 100 measures platelet adhesion & aggregationPFA – 100 measures platelet adhesion & aggregation APTTAPTT Normal is 25-40 secsNormal is 25-40 secs Determines abnormality of intrinsic clotting pathwayDetermines abnormality of intrinsic clotting pathway Prolonged in factor VIII , IX , HMWK , PK , XII , XI , X, V , Prolonged in factor VIII , IX , HMWK , PK , XII , XI , X, V ,

II and by inhibitorsII and by inhibitors PTPT Normal – 12 – 14 Secs.Normal – 12 – 14 Secs. Extrinsic pathwayExtrinsic pathway Prolonged deficiency of factor VII , X , V , II , fibrinogen & Prolonged deficiency of factor VII , X , V , II , fibrinogen &

inhibitors of these factorsinhibitors of these factors

THROMBIN CLOTTING TIMETHROMBIN CLOTTING TIME Normal 11 – 15 SecsNormal 11 – 15 Secs Measures thrombin induced conversion of Measures thrombin induced conversion of

fibrinogen to fibrin fibrinogen to fibrin Abnormal in hypofibrinogenemia, Abnormal in hypofibrinogenemia,

afibrinogenemia,dysfibrinogenemia afibrinogenemia,dysfibrinogenemia inhibitors.inhibitors.

REPTILASE TIMEREPTILASE TIME Uses snake venom to clot fibrinogenUses snake venom to clot fibrinogen Not sensitive to heparinNot sensitive to heparin Prolonged only by reduced or Prolonged only by reduced or

dysfunctional fibrinogen & FSPdysfunctional fibrinogen & FSP

MIXING STUDIESMIXING STUDIES Unexplained prolongation of PT,APTT or TTUnexplained prolongation of PT,APTT or TT Normal plasma is added to patient’s plasma, PT or APTT is Normal plasma is added to patient’s plasma, PT or APTT is

repeated.repeated. Correction of PT or APTT by 1:1 mixing suggests deficiency Correction of PT or APTT by 1:1 mixing suggests deficiency

of a clotting factor.of a clotting factor. If not / partially corrected, an inhibitor is present ( Heparin )If not / partially corrected, an inhibitor is present ( Heparin ) If clinical bleeding seen ,inhibitor of a specific clotting factor If clinical bleeding seen ,inhibitor of a specific clotting factor

VIII, IX or XI maybe present.VIII, IX or XI maybe present. PTT prolonged, mixing study prolonged, no clinical bleed – PTT prolonged, mixing study prolonged, no clinical bleed –

lupus like anticoagulant.lupus like anticoagulant. BETHESDA ASSAY ( To determine inhibitors )BETHESDA ASSAY ( To determine inhibitors ) One Bethesda unit is defined as the amount that will inhibit One Bethesda unit is defined as the amount that will inhibit

50 % of clotting factor in normal plasma50 % of clotting factor in normal plasma

BLEEDING TIMEBLEEDING TIME Normal 4 – 7 MinNormal 4 – 7 Min Assesses function of platelets & interaction with the vascular wall.Assesses function of platelets & interaction with the vascular wall. Prolonged in thrombocytopenia, qualitative defect of plateletsProlonged in thrombocytopenia, qualitative defect of platelets CLOT RETRACTIONCLOT RETRACTION Retraction & exudation of serum after one hour is observed in Retraction & exudation of serum after one hour is observed in

clotting tube.clotting tube. FACTOR ASSAYFACTOR ASSAY Measured using factor deficient plasma.Measured using factor deficient plasma. Activity measured against a standard where 100% activity is Activity measured against a standard where 100% activity is

expressed as 100 IU / DLexpressed as 100 IU / DL 1 IU of each factor is defined as that amount in 1ml of normal 1 IU of each factor is defined as that amount in 1ml of normal

plasma referenced against WHO standard.plasma referenced against WHO standard. Normal range 50 – 150 IU / DLNormal range 50 – 150 IU / DL Severe deficiency of VIII & IX - < 1IU/DLSevere deficiency of VIII & IX - < 1IU/DL Moderate – 1 – 5 IU /DLModerate – 1 – 5 IU /DL Mild - > 5 IU /DLMild - > 5 IU /DL

PLATELET AGGREGATIONPLATELET AGGREGATION

PRP from patient is activated with PRP from patient is activated with agonists-agonists-ADP,epinephrine,collagen,thrombin,ADP,epinephrine,collagen,thrombin,ristocetinristocetin

TESTS FOR XIII-clot solubility in TESTS FOR XIII-clot solubility in 5Murea,when the PT and PTT both 5Murea,when the PT and PTT both are normal, but there is a strong are normal, but there is a strong bleeding historybleeding history

PROLONGED PTTPROLONGED PTTNo clinical bleeding-XII,HMWK,PKNo clinical bleeding-XII,HMWK,PKMild or rare bleeding-XIMild or rare bleeding-XIFrequent, severe bleeding-VIII&IXFrequent, severe bleeding-VIII&IX PROLONGED PTPROLONGED PTVII deficiencyVII deficiencyVit k def-earlyVit k def-early PROLONGED PTT&PTPROLONGED PTT&PTII&V or X deficiencyII&V or X deficiencyVit k-lateVit k-lateCoumarin,mild hepatic diseaseCoumarin,mild hepatic disease PROLONGED THROMBIN TIMEPROLONGED THROMBIN TIMEMild or rare bleeding- afibrinogenemiaMild or rare bleeding- afibrinogenemiaFrequent ,severe bleeding- dysfibrinogenemiaFrequent ,severe bleeding- dysfibrinogenemiaHeparin like inhibitorsHeparin like inhibitors PROLONGED PT & or PTT NOT CORRECTED WITH NORMAL PLASMAPROLONGED PT & or PTT NOT CORRECTED WITH NORMAL PLASMA Specific or non specific inhibitors syndromeSpecific or non specific inhibitors syndrome CLOT SOLUBILITY IN 5M UREACLOT SOLUBILITY IN 5M UREA Factor XIII deiciencyFactor XIII deiciency

PRIMARY HEMOSTATIC PRIMARY HEMOSTATIC DISORDERDISORDER

DEFECTS OF PLATELET ADHESIONDEFECTS OF PLATELET ADHESION Von Willebrand’s diseaseVon Willebrand’s disease Bernard Soulier syndrome ( Absence of GP I Bernard Soulier syndrome ( Absence of GP I

b / IX)b / IX) DEFECTS OF PLATELET AGGREGATIONDEFECTS OF PLATELET AGGREGATION Glanzmann’s thrombasthenia ( GP II b / III Glanzmann’s thrombasthenia ( GP II b / III

a )a ) DEFECTS OF PLATELET RELEASEDEFECTS OF PLATELET RELEASE Decreased cyclooxygenase activity.Decreased cyclooxygenase activity. Drug induced Drug induced Storage pool defectStorage pool defect UremiaUremia

BLEEDING DISORDER BLEEDING DISORDER WITH NORMAL WITH NORMAL

SCREENINGSCREENING Senile purpuraSenile purpura Simple purpuraSimple purpura Factor XIIIFactor XIII Alpha 2 antiplasmin defAlpha 2 antiplasmin def AmyloidosisAmyloidosis Pender osler weber syndromePender osler weber syndrome ScurvyScurvy Ehler danlosEhler danlos Mild factor deficiencyMild factor deficiency