medicine.Bleeding disorders.(dr.sabir) (new powerpoint)

Bleeding Bleeding DisordersDisorders

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

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 tis. Mucous membranes (joints, musc)

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 tests for bleeding Screening tests for bleeding disordersdisorders

Test Abnormality detectedBlood count and Anaemia, leukaemia, DICfilm

Platelet count ThrombocytopeniaaPTT Def. of all coagulation factors except

VII, esp. follows VIII and IX; heparinPT Def. of F I, II, V, VII, and X; warfarin

Thrombin time or Hypo-, dysfibrinogenaemia; heparin fibrinogen FDPs Bleeding time Test of platelet-vessel wall interaction

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

ThrombocytopeniaThrombocytopeniaThe lifespan of a platelet is 7-10 days and the normal count for all ages is 150000-450000Once released from the BM young platelets are trapped in the spleen for up to 36 hours before entering the circulation, where they have a primary haemostatic role.

Congenital abnormalities of platelets can be divided into disorders of platelet production and those of platelet function. All are very rare. In general they cause moderate to severe bleeding problems.

Acquired thrombocytopeniaAcquired thrombocytopeniaDecreased production of platelets due to suppression or failure of the BM is the commonest cause of thrombocytopenia. In aplastic anaemia, leukaemia and marrow infiltration, and after chemotherapy, thrombocytopenia is usually associated with a failure of red and white cell production but may be an isolated finding secondary to drug toxicity (penicillamine, cotrimoxazole), alcohol, or viralinfection (HIV, infectious mononucleosis). Viral infection is the most common cause of mild transient thrombocytopenia

Acquired…contAcquired…contIncreased platelet consumption may be due to immune or non-immune mechanisms.

Post-transfusion purpura (PTP) is a rare complication of blood transfusion. It presents with severe thrombocytopenia 7-10 days after the transfusion and usually occurs in multiparous women who are negative for the human platelet antigen 1a (HPA1a).Antibodies to HPA1a develop, and in some way this alloantibody is responsible for the immune destruction of autologous platelets.

Neonatal alloimmune thrombocytopenia (NAITP) is similar to haemolytic disease of the newborn except that the antigenic stimulus comes from platelet specific antigens rather than redcell antigens. In 80% of cases the antigen is human platelet antigen 1a, and mothers negative (about 5% of the population) for this antigen form antibodies when sensitised by a fetus positive for the antigen. Fetal platelet destruction results from transplacental passage of these antibodies and severe bleeding, including intracranial haemorrhage, can occur in utero.

Heparin-induced thrombocytopenia (HIT) occurs during unfractionated heparin therapy in up to 5% of patients, but is less frequently associated with low molecular weight heparins. It may become manifest when arterial or venous thrombosis occurs during a fall in the platelet count and is thought to be due to the formation of antibodies to heparin that are bound to platelet factor 4. The immune complexes activate platelets and endothelial cells, resulting in thrombocytopenia and thrombosis coexisting. Heparin-induced thrombocytopenia carries an appreciable mortality risk if the diagnosis is delayed.

In thrombotic thrombocytopenic purpura (TTP) the presenting features can be fever, fluctuating neurological signs, renal impairment, and intravascular haemolysis, resulting in thrombocytopenia.

The condition is suspected clinically by thrombocytopenia, red cell fragmentation on the blood film, and a reticulocytosis.

Causes of acquired Causes of acquired platelet dysfunctionplatelet dysfunction

•Aspirin and NSAIDs •Penicillins and cephalosporins

•Uraemia •Alcohol

•Liver disease •Myeloproliferative disorders

•Myeloma •Cardiopulmonary bypass

•Fish oils

Increased consumption of Increased consumption of plateletsplatelets

•Disorders with immune mechanism:Autoimmune: ITPAlloimmune: post-transfusion purpura, neonatalalloimmune thrombocytopeniaInfection associated: infectious mononucleosis, HIV,malariaDrug induced: heparin, penicillin, quinine, rifampicin,sulphonamides

•TTP/HUS •Hypersplenism and splenomegaly

•DIC •Massive transfusion

Treatment of platelet Treatment of platelet disordersdisorders

Congenital disorders:

•Platelet transfusions (leucodepleted, HLA compatible and irradiated)

•DDAVP •Tranexamic acid

•Recombinant factor VIIa •Bone marrow transplantation

Treatment…contTreatment…contAcquired disorders

•Bone marrow failurePlatelet transfusions if platelet count 10000

•ITP (adults)PrednisoloneIntravenous immunoglobulinSplenectomy

•Post-transfusion purpuraIntravenous immunoglobulinPlasma exchange

•Heparin-induced thrombocytopeniaAnticoagulation but without heparin

•Thrombotic thrombocytopenic purpuraLarge volume plasma exchangeAspirin when platelets 50000

Treatment…contTreatment…cont •DIC:

Treat underlying causeFresh frozen plasmaPlatelet transfusion

•HypersplenismSplenectomy if severe

•Platelet function disordersPlatelet transfusionDDAVP

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 systemASSOCIATIONS—neoplasm (CLL, lymphoma), infections (HIV), autoimmune (SLE)

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.

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 tapering. Platelet recovery occurs within 3 weeks in 2/3 of pts. If platelet count did not increase after 4 weeks of treatment, consider splenectomyPLT transfusion and IVIg 1 g/kg IV daily 1–2 days, indicated in life-threatening bleeding. If the pt 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 1gIV dailyX3 days. 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 12hr.

It is X-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

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

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

endothelium

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

Factor VIII concentrate Virally inactivated product

Common clinical conditions associated Common clinical conditions associated with DICwith DIC

Sepsis (Escherichia coli,

N. meningitidis, malaria(

Trauma: Head injury, Fat embolism

Malignancy lung,prostate,pancreatic

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

PathophysiologyPathophysiologydamage to endothelium →release of tissue factor → massive activation ofcoagulation cascade → intravascular coagulation and depletion of clotting factors

FeaturesFeaturesmicroangiopathic hemolytic anemia, thrombocytopenia, bleeding, thrombosis, ischemia. ↑INR, ↑ PTT, ↓ fibrinogen (although it can be normal or even elevated), ↓ factor VIII (in contrast to liver diseases, which have normal factor VIII). Schistocytes on peripheral smear

TreatmentTreatmenttreat underlying cause and complications (hypoxia, dehydration, acidosis, acute renal failure). Replete coagulation factors if bleeding (FFP 2 U, cryoprecipitate 10 U). Anticoagulation if thrombosis (consider IV heparin)

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 Replacement therapy