Bleeding Bleeding DisordersDisorders

By Dr. Sabir M. AmeenBy Dr. Sabir M. Ameen

VasoconstrictionVasoconstriction

1°1° HemostasisHemostasis

2°2° HemostasisHemostasis

HemostasisHemostasis

BV Injury

PlateletPlateletAggregation

PlateletActivation

Blood VesselBlood Vessel Constriction

CoagulationCoagulation Cascade

Stable Hemostatic Plug

Fibrin formation

Reduced

Blood flow

Tissue Factor

Primary hemostatic plug

Neural

Lab Tests•CBC-Plt•BT,(CT)•PT•PTT

Plt StudyMorphologyFunctionAntibody

HistoryHistory1 .Site of bleeding:

*Muscle & joint bleeds indicate a coagulation defect

*purpura, prolonged bleeding from superficial cuts, epistaxis, GI bleeding, menorrhagia, indicate PLT disorder, thrombocytopenia or vW disease

HistoryHistory2 .Duration: congenital or acquired

3 .Precipitating cause: if spontaneous indicate severe defect

4 .surgery: dental extraction, tonsillectomy, circumcision. Bleeding immediately after surgery indicate defective PLT plug formation. Bleeding after some hours indicate failure of PLT plug stabilisation by fibrin due to coagulation defect.

HistoryHistory5 .Family history :

*Hereditary or acquired *Negative history does not exclude a

hereditary cause, as e.g: about 1/3 of cases of hemophilia have negative family history (mutations).

6 .Systemic disease :

Hepatic or renal failureCT disease

historyhistory7 .Drugs: almost any drug can

potentially produce bleeding( cytotoxics. NSAIDs…etc)

ExaminationExaminationLook for: 1. anemia: BM failure, leukemia

2 .purpura, bruises, bleeding in mouth3 .Telangiectasia of lips (HHT)

4 .LN enlargement: leukemia, viral ( ITP)5 .Stigmata of chronic liver disease: spider

nevi, clubbing, palmar erythema…etc6 .Fundal examination

Clinical Features of Bleeding DisordersClinical Features of Bleeding Disorders

Platelet Coagulation disorders fac disorders

Site of bleeding Skin Deep in soft tissues Mucous membranes (joints, musc) (epistaxis, gum, vaginal, GI tract)

Petechiae Yes No

Ecchymoses (“bruises”) Small, superficial Large, deep

Hemarthrosis / muscle bleeding Extremely rare Common

Bleeding after cuts & scratches Yes No

Bleeding after surgery or trauma Immediate, Delayed1-2 d usually mild often severe

Platelet CoagulationPlatelet Coagulation

Petechiae, Purpura Hematoma, Joint bl.

PetechiaePetechiae

Do not blanch with Do not blanch with pressurepressure

(cf. angiomas) (cf. angiomas)Not palpableNot palpable

(cf. vasculitis) (cf. vasculitis)

(typical of platelet disorders)

HemarthrosisHemarthrosis

HematomaHematoma

PetechiaePetechiae

PurpuraPurpura

EcchymosisEcchymosis

Screening testsScreening tests1 .PLT count: thrombocytopenia

2 .Bleeding time( normal <8 min.): î in thrombocytopenia, PLT dysfunction, decreased vWF, vascular abnormality

3 .PT: factors II, V, VII, X deficiency4 .PTT: factors II, V, VIII, IX, X, XI, XII

deficiency, heparin therapy, Abs against clotting factors, lupus anticoagulant

5 .fibrinogen: hypofibrinogenemia

Causes of bleedingCauses of bleeding1 .Thrombocytopenia:

a- viral infectionsb- drug-inducedc- B12 or folate deficiencyd- ITP, DIC, TTP/HUS ( consumption)e- BM infiltration: leukemia, MM, Ca, myelofibrosis

Causes..contCauses..cont..

2 .Clotting factor deficiency:

a- liver diseaseb- drugs: warfarin, heparinc- consumption: DICd- dilution: massive blood transfusione- congenital: hemophilia..etcf- vit K deficiency: e.g, malabsorption

Causes…contCauses…cont..3 .CT atrophy :

a- old ageb- steroid therapyc- wasting

4 .Vessel wall disorders :A- aspirinB- Osler-Weber Rendu diseaseC- angiodysplasia

Idiopathic thrombocytopenic Idiopathic thrombocytopenic purpura(ITP)purpura(ITP)

It is due to auto- antibodies directed against PLT membrane glycoprotein IIb-IIIa which causes premature removal of PLTs by the monocyte-macrophage system

ITPITPC/F: 1. in children: sudden onset of purpura, oral or nasal bleeding, usually 2-3 wk after a viral illness

2 .In adults: affects females more, with insidious onset, usually not associated with viral infection, but may be associated with CT disease.It is characterised by remission and relapse.

ITPITPLAB.

1 .CBC: reduced PLT count2 .BM: increased megakaryocytes

managementmanagement1 .In children: usually it is self-limiting,

if severe purpura or epistaxis, or PLT <10000 give steroids ( prednisolone 2mg/kg/d)If pesistent epistaxis GI bleeding, retinal hemorrhage : give PLT transfusion and IV IgG

managementmanagement2 .In adults: prednisolone 1 mg/kg/d for 3-4

wk then gradually tapered over 6-8 wk, relapse may occur on taperingPLT transfusion and IVIg indicated in life-threatening bleeding. If the patient has two relapses , splenectomy is indicated, which is curative in 70% of patients, in the remainder the aim is to keep the patient free of symptoms rather than to raise level of PLT( e.g 5mg/d of prednisolone may be sufficient)

managementmanagementIn severe cases iv methylpredinsolone with or without IVIg may be givenIf still not controlled give immunosuppressive drugs e.g: vincristine, cyclophosphamide

Hemophilia AHemophilia AFactor VIII is synthesized mainly by liver , but also by spleen, kidney, and placenta, carried by vWF, half-life in plasma is 12 hr.It is sex-linked recessive and affects about 1/10000, thus all daughters of hemophiliacs are carriers and 50% of sisters are carriers. If a carrier has a son, he has 50% chance of having hemophilia and a daughter has 50% chance of being a carrier

Hemophilia AHemophilia AC/FAt around 6 mon. child develop bruises and hemarthrosis as he starts to move around.

Normal level of factor VIII is 50%-150%, and severity is measured according to this level:

1 .severe: <1% F VIII or IX: liable for spontaneous hemarthrosis & muscle hematoma

Hemophilia AHemophilia A2 .Moderate : 1-5% F VIII or IX: mild

trauma or surgery causes hematoma3 .mild: 6-50% F VIII or IX: major

surgery or injury results in excess bleeding.Joints commonly affected include: knees, elbows, ankles, and hips.They look hot, swollen, and very painfull and tender.

Hemophilia AHemophilia AWith recurrent bleeding there will be synovial hypertrophy, destruction of cartilage and secondary osteoarthritis,In muscles : calf, psoas: bleeding lead to ischemia, necrosis, fibrosis which will lead to contracture & shortening of tendons e.g achilles tendon making walking difficult.

Shortening of Achilles Shortening of Achilles tendontendon

Dosing guidelines for hemophilia ADosing guidelines for hemophilia AMild bleeding :

Target: 30% dosing q8-12h; 1-2 days (15U/kg)Hemarthrosis, oropharyngeal or dental, epistaxis, hematuria

Major bleeding:Target: 80-100% q8-12h; 7-14 days (50U/kg)CNS trauma, hemorrhage, lumbar punctureSurgeryRetroperitoneal hemorrhageGI bleeding

Adjunctive therapy : -aminocaproic acid or DDAVP (for mild disease only)

Von Willebrand’s diseaseVon Willebrand’s diseaseUsually it is a mild bleeding disorder of many types, the commonest being type I which is autosomal dominant.

vWF is synthesized by endothelial cells and megakaryocytes and has two functions: 1. carrier for F VIII and 2. form bridges between PLT and subendothelial collagen

vW DisvW Dis..

C/FBruising, epistaxis, menorrhagia, GI bleedingLAB

*Decreased level of vWF, increased bleeding time, increased PTT

Treatment of von Willebrand DiseaseTreatment of von Willebrand Disease

Cryoprecipitate Source of fibrinogen, factor VIII and VWF

Only plasma fraction that consistently contains VWF multimers

DDAVP (deamino-8-arginine vasopressin) plasma VWF levels by stimulating secretion from

endothelium Duration of response is variable

Not generally used in type 2 disease Dosage 0.3 µg/kg q 12 hr IV

Factor VIII concentrate (Intermediate purity) Virally inactivated product

Common clinical conditions associated Common clinical conditions associated with DICwith DIC

Sepsis

Trauma: Head injury, Fat embolism

Malignancy

Obstetrical complications:

Amniotic fluid embolismAbruptio placentae

Vascular disorders

Reaction to toxin (e.g. snake venom, drugs)

Immunologic disordersSevere allergic reactionTransplant rejection

Activation of both coagulation and fibrinolysisTriggered by

Pathogenesis of DICPathogenesis of DIC

Coagulation Fibrinolysis

Fibrinogen

FibrinMonomers

FibrinClot

(intravascular)

Fibrin(ogen)Degradation

Products

Plasmin

Thrombin Plasmin

Release of thromboplastic

material intocirculation

Consumption ofcoagulation factors;

presence of FDPs aPTT PT TT

Fibrinogen

Presence of plasmin FDP

Intravascular clot Platelets

Schistocytes

DICDICTreatment approachesTreatment approaches

Treatment of underlying disorder

Anticoagulation with heparin

Platelet transfusion

Fresh frozen plasma

Coagulation inhibitor concentrate (ATIII)

Management of Hemostatic Management of Hemostatic Defects in Liver DiseaseDefects in Liver Disease

Treatment for prolonged PT/PT Vitamin K 10 mg x 3 days - usually ineffective

Fresh-frozen plasma infusion (1200-1500 ml) immediate but temporary effect

Treatment for low fibrinogen Cryoprecipitate (1 unit/10kg body weight)

Treatment for DIC (↑ D-dimer, ↓ factor VIII, thrombocytopeniaReplacement therapy