Bleeding Disorders

Dr. Farjah H.AlGahtaniDr. Farjah H.AlGahtaniAssistant Professor of Internal Medicin,Consultant HematologyDirector of transfusin Medicin and Blood Bank Department,KSU

Hemostasis

BV Injury

PlateletPlateletAggregation

PlateletActivation

Blood VesselBlood Vessel Constriction

CoagulationCoagulation Cascade

Stable Hemostatic Plug

Fibrin formation

Reduced

Blood flow

Damage/contact.

Primary hemostatic plug

Neural

•CBC-Plt•BT,(CT)•PT•PTT

Platelet studyAntibody testsFactor Assay

Contact

HEMOSTASISPrimary 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

• Scurvy, senile purpura, Henoch-Schonlein syndrome.

• Disorders of Platelets• Thrombocytopenia ITP, TTP, HUS, DIC.

• Aspirin therapy, Thrombasthenia,

• Disorders of Coagulation• Extrinsic, intrinsic, combined.

• Other disorders• Post transfusion purpura, MPS, MDS.

Tests of Hemostasis:

Screening tests: Bleeding.T - 10m. Platelet & BV function Prothrombin.T – Extrinsic, aPTT – Instrinsic Thrombin.T – common path. (DIC)

Specific tests: Factor assays – hemophilia. Tests of thrombosis – TT, FDP, DDA, Platelet function studies:

Adhesion, Aggregation, Release tests. Bone Marrow study

Bleeding: Clinical Features

Local - Vs - General, spontaneous. .

Hematoma / Joint Bleeds- CoagSkin / Mucosal Bleeds – PLTwound / surgical bleeding – Immediate - PLT Delayed - Coagulation

PlateletCoagulation

Petechiae, Purpura Hematoma, Joint bl.

Vascular disorders:

Petechiae, purpura, ecchymosessenile purpuravitamin C deficiency (scurvy)Connective tissue disordersInfections – MeningococcusHenoch-Schonlein Purpura-Immu

Senile PurpuraSenile Purpura

Petechiae in Petechiae in VasculitisVasculitis

(Rocky Mountain Spotted Fever)(Rocky Mountain Spotted Fever)

Henoch-Schonlein purpuraImmune

disorderChildrenFollows

infectionPetechiae with

edema and itching.

Henoch-Schonlein purpura

20y Male, fever, painful symmetric polyarthritis for a day. During the next two days, edema and palpable purpura developed.

Platelet Disorders - Features:

Mucocutaneous bleedingPetechiae, Purpura, Ecchymosis.

spontaneous bleeding after trauma

CNS bleeding (severe plt)Prolonged bleeding time (BT)

BLEEDING TIME vs. PLATELET COUNT

0

50

100

150

200

250

300

350

400

3.5 4 4.5 5 5.5 7 9 12 15 25 30

Minutes

Pla

tele

t co

un

t (x

100

0)

Idiopathic Thrombocytopenic Purpura (ITP)

Acute - children (post infection)Chronic - adults ( females, 20-40 yrs)autoimmune disorder antiplatelet antibodies (IgG)IgG coated platelets removed by spleenUsually megakaryocytes in BM

Platelet dysfunction:Inherited Disorders: Bernard-Soulier disease

large platelets, failure of adhesionGlanzmann’s thrombasthenia

normal size, failure of aggregation

Acquired Disorders:Drugs - Aspirin, Alcohol, Uremia,

Platelet Aggregation CurvesPlatelet Aggregation Curves

Von-Willebrand Disease:Coagulation + PLT disorder:Congenital disorderDeficiency of vWF molecule Part of FVIII, Mediates platelet adhesionProlonged Bleeding timeLow Factor VIII & long aPTTMucocutaneous bleeding

Von-Willebrand Disease

vWF: F-VIII & PLT function.

Defective Platelet Adhesion

Skin Bleeding Prolonged Bleeding

time.Low Factor VIII levels.

Coagulation disorders: Deficiencies of Clotting factors

Onset - delayed after traumaDeep bleeding

Into joints - Hemarthroses Into deep tissues – Hematoma large skin bleed – Ecchymoses

Blood Coagulation & TestsBlood Coagulation & Tests

CT- Large hematoma of psoas muscleCT- Large hematoma of psoas muscle

Coagulation DisordersLaboratory findings:Normal bleeding time & Platelet countProlonged 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 DeficiencyClassic hemophilia (hemophilia A)X-linked disorder (affects 1º males)Most common - severe bleedingSpontaneous hematomas < 1, 5, 75%Abnormal aPTT – Intrinsic path.Diagnosis - factor VIII assayTreatment - factor VIII concentrateCryoprecipitate (less desirable)

Factor IX DeficiencyChristmas disease (Hemophilia B)X-linked recessive disorder Indistinguishable from classic

hemophilia (F VIII)Requires evaluation of factor VIII and IX

activity levels to diagnoseTreatment - factor IX concentrateCryoprecipitate if factor IX unavailable

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 BT Plt PT PTT

Vascular Dis - - - -

PLT Disorder - - - -

Factor 8/9 *Congenital - - -

Vit K / Liver*Acquired - - -

Combined (DIC) -

Summary

Symptom Platelet Coagulation Petechiae Yes No

Sites Skin & Mucosa

Deep Tissue

Time Immediate Delayed

Ecchymoses/Hematomas

Yes Yes

CLL-Thrombocytopenia

Lymphoid cells

Smear cells

(Fragile)

Dengue Hemorrhagic fever

Platelet deficiency..

Thrombocytopenia-TTP

Summary

Complex system to keep blood fluidTo block leakage on injury.BV, PLT & CoagulationComplex inhibitory mechanismsComplex thrombolysis mechanisms.Screening tests: BT, CT (PT, aPTT)Special tests: Factor assay, PLT function etc.

Disorders of Hemostasis

Vascular disorders – Scurvy, easy bruising, Henoch-Schonlein purpura.

Platelet disorders Quantitative - Thrombocytopenia Qualitative - Platelet function disorders –

GlanzmansCoagulation disorders

Congenital - Haemophilia (A, B), Von-Willebrands

Acquired - Vitamin-K deficiency, Liver diseaseMixed/Consumption: DIC