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
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