Primary Hemostasis:

?Blood vessel contraction

?Platelet Plug Formation

Secondary Hemostasis:

?Activation of Clotting Cascade

?Deposition & Stabilization of Fibrin

Tertiary Hemostasis:

?Dissolution of Fibrin Clot

?Dependent on Plasminogen Activation

Classification:

?Disorders of Blood vessels

?Disorders of Platelets

?Disorders of Coagulation

?Other disorders

Tests of Hemostasis

Non specific tests:

?Bleeding.T - To test Platelet & BV function

?Prothrombin.T ? Extrinsic, liver, warfarin

?APTT ? Instrinsic

?Thrombin.T ? Both paths. (DIC), heparin

Specific tests:

?Factor assays ?

?Tests of thrombosis ? TT, FDP, DDA,

?Platelet function studies:

?Adhesion, Aggregation, Release & PG pathway tests.

?Bone Marrow study

Bleeding: Clinical Features

?Local - Vs - General, spontaneous . .

?Hematoma / Joint Bleeds- Coag

?Skin / Mucosal Bleeds ? PLT

?wound / surgical bleeding ?

?Immediate - PLT

?Delayed - Coagulation

Platelet Coagulation

Platelet Disorders - Features:

?Mucocutaneous bleeding

?Petechiae, Purpura, Ecchymosis.

?spontaneous bleeding after trauma

?CNS bleeding (severe ? plt)

?Prolonged bleeding time (BT)

BLEEDING TIME vs. PLATELET COUNT

VON WILLEBRAND'S DiSEASE

?Most common congenital disorder

?Defective or deficient vWF, that mediates platelet adhesion

?Factor synthesized in ???

?Function --- plt adhesion, binds factor VIII and protect it from degradation

?Rarely this def can cause elevated PTT d/t low factor VIII

?vWD type I (80%) (AD)

?vWD type II ( a and b )

?vWD type III (AR)

?Pseudo vWD

?S/S

?Mild

?Musocal

?Rarely posttraumatic or surgical

?Exacerbated by aspirin, relieved by preg or estr use

Lab findings:

?BT usually prolonged

?vWF assays, factor VIII antigen or ristocetin

?Platelet aggregation studies

?Usually nothing apart from being cautious using aspirin

?Mx.

?Mild ? desmopressin 0.3ug/kg effect within 90mins Q24hrly

?Severe persistent - factor VIII conc.

?Humate- P 20-50U/kg

?AFA as adjuvant therapy given for a week after desmo or cryo to reduce likelihood of bleeding

Coagulation disorders:

?Deficiencies of Clotting factors

?Onset - delayed after trauma

?Deep bleeding

?Into joints - Hemarthroses

?Into deep tissues ? Hematoma

?large skin bleed ? Ecchymoses

Coagulation Disorders

Laboratory findings:

?Normal bleeding time & Platelet count

?Prolonged prothrombin time (PT)

?deficiencies of II, V, VII, X

?Prolonged time (aPTT)

?all factors except VII, XIII

?Mixing studies - normal plasma corrects PT or aPTT

Factor VIII Deficiency:

?Classic hemophilia (hemophilia A)

?X-linked disorder (50% daughters carriers 50% sons hemophiliac)

?antenatal dx CVS (11) Amnio (16)

?Most common presentation - severe bleeding -- hemearthross (knees, elbows,ankles, hips)

?Spontaneous hematomas (calf , psoas)

?any site incl. Intracranial --> fatal

Hemophilia A:

?Most common severe coagulation disorder throughout the world

?2nd to vWD among all disorders

?Deficiency of factor VIII ( females least likely to be affected, unless she hs a hemophilic father and a carrier mother)

?S/s

?Spontaneous hemarthroses is so classical that its almost diagnostic of the disease esp if a positive family history is also present

?Seropositivity for HIV via factor VIII concentrates

Lab findings:

?Abnormal aPTT ? Intrinsic path.

?PT,BT,vWF normal

?Diagnosis - factor VIII assay

Treatment:

?Factor VIII concentrate (to stop bleeding & B4 surgery)

?Now heat treated (free of HIV)

?Recombinant factor VIII

?Amount depends on the desired level of correction

?I U of Factor VIII ? I ml of plasma 40U/kg to acheinve 100% levels ( usually before surgery

?Distribution factor of favtor VIII is 1.5 = 60u/kg

?For young adult 4000 U/kg followed by 2000 U ( 30U/kg)

?Q12hrly

I/V desmopressin (mild):

?Cryoprecipitate (less desirable)

?Pts on desmo/cryo treat with ACA(Emicar) 4gOD x 4d

Prognosis:

?VIII has improved prognosis

?Limited functional ability due to joint immobility 20 to joint bleeds

?Hep infection

?Resistance to factor VIII

Factor IX Deficiency:

?Christmas disease (Hemophilia B)

?X-linked recessive disorder

?Indistinguishable from classic hemophilia (F VIII)

?Spontaneous hemarthrosis

?Coagulation factor IX def

?2/3rd quantitative defect

?Reduced factor IX in blood, prolonged PTT

Management:

?Factor IX concentrates

?80U/kg achieve 100% levels of the factor

?T1/2 is 18 hrs, in major surgeries maintain 40U/kg every18hrs

?Increased risk of thrombosis with this ttx

?No role of desmo

Secondary Hemostatic Disorders

?Acquired coagulation disorder:

?Vitamin K deficiency

-neonates - decreased intestinal

?flora and dietary intake

-oral anticoagulants (coumadin)

-fat malabsorption syndromes

?Required for factors II, VII, IX, X

?Prolonged PT and aPTT

Combined Primary and Secondary Hemostatic Disorders (DIC):

?Disseminated Intravascular Coagulation

?Major pathologic processes -

?obstetric complications, neoplasms, infection (sepsis), major trauma

?Primary - platelet consumption

?(? bleeding time, ? platelets)

?Secondary - factor consumption

?(? PT, aPTT)

Combined Primary and Secondary Hemostatic Disorders:

?Severe Liver Disease

?Primary - dysfunctional platelets and/or thrombocytopenia (? BT)

?Secondary - decrease in all coagulation factors except vWF (? PT, aPTT)

?Vitamin K will promote synthesis of factors II, VII, IX, X

Summary Hemostatic Disorders:

oBTPltPTPTT

?Vascular Dis - ? - - -

?PLT Disorder - ? - ? - -

?Factor 8/9

?*Congenital - - - ?

?Vit K / Liver

?*Acquired - - ? -?

?Combined (DIC) ? ? -? ?

?Summary

Hemophilia in Pakistan:

?A relatively young country, with an ancient past, Pakistan achieved independence from Britain on August 14, 1947, after its bloody partition from India.

?Pakistan's health care system has crumbled: public hospitals are in appalling condition, even basic treatment unavailable for many common disorders.

? Private hospitals-modern and fully equipped-foster the only available research, and provide the most advanced and comprehensive care for people with hemophilia, but are extremely expensive and beyond the reach of most.

?No infrastructure currently exists to provide public and free care to people with this lifelong bleeding disorder.

?Of the estimated 12,000 people with hemophilia in Pakistan, only 3,100 have been identified.

?Until early 1980, hemophilia was not even known to exist within the country, and only a few patients were alive. In 1982 the first blood bank was formed.

?Currently only five major cities-Karachi, Lahore, Rawalpindi-Islamabad, Peshawar Multan, Faisalabad and Quetta-now have facilities to provide plasma or cryo.

?And treatment at its best in Pakistan is still primitive by Western standards. Virally inactivated high or intermediate purity factor concentrates are available only to the minority elite, who are wealthy enough to pay out of pocket. But the majority of patients, the poor, receive plasma or cryo. They most often receive inferior plasma, which is not always screened for HBV, HCV and HIV.

?The results-

?Inferior factor replacement,

?lack of patient and physician education regarding simple techniques (application of ice or ice packs, immobilization of affected joints, use of slings), and lack of physiotherapy facilities-

?have contributed to the physical disability and crippling arthropathy of people with hemophilia.

?50% percent of patients suffer from chronic hemophilic arthropathy.

?90% of those receiving treatment are infected with HCV.

?Only a handful developed AIDS during the last 15 years because the population was spared from the epidemic that swept developed countries, but most of those infected with HIV have died.

?Tragically, many with hemophilia die early from intracranial hemorrhage, infection or circumcision.

?Indeed, in this Muslim country where circumcision is required, approximately one-third of patients have a family history of bleeding to death after circumcision.