FKG minggu 2

8/2/2019 FKG minggu 2

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Bleeding Disorders

Indra Wijaya

Internal MedicineHasan Sadikin Hospital - Medical FacultyPadjadjaran University


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Objectives

Coagulation factor disorders and treatment

Disorders of platelets and platelettransfusion

Adjunctive drug therapy for bleeding


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Objectives

Coagulation factor disorders andtreatment




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Coagulation factor disorders

Inherited bleedingdisorders

Hemophilia A and B

vonWillebrands diseaseOther factor

deficiencies

e.g: Factor XI deficiency,etc

Acquired bleedingdisorders

Liver disease

Vitamin K deficiency/Warfarin overdose

DIC


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Hemofilia


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Hemophilia A and BHemophilia A Hemophilia B

Coagulation factor deficiency Factor VIII Factor IX

Inheritance X-linked X-linkedrecessive recessive

Incidence 1/10,000 males 1/50,000 males

Severity Related to factor level


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Hemophilia

Clinical manifestations (hemophilia A & B

indistinguishable)

Hemarthrosis (most common)

Fixed jointsSoft tissue hematomas (e.g., muscle)

Muscle atrophy

Shortened tendons

Other sites of bleeding

Urinary tract

CNS, neck (may be life-threatening)


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Factor VIII concentrate or Recombinant(Koate/Kogenate)

Dosage based on desired factor VIII increase (%):

Body weight (kg) x 0.5 int. units/kg x desired factor

VIII increase (%) = int. units factor VIII required

For example: 50 kg x 0.5 int. units/kg x 30 (% increase) =

750 int. units factor VIII

Dosage based on expected factor VIII increase (%):

(# int. units administered x 2%/int. units/kg) dividedby body weight (kg) = expected % factor VIII increase

For example: (1400 int. units x 2%/int. units/kg) divided by 70


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General Guidelines F VIIIconcentrate/recombinant

Minorhemorrhage: 10-20int. units/kg as a

single dose toachieve FVIII


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Treatment of hemophilia B

Agent

High purity factor IX

Recombinant human factor IX

DoseInitial dose: 100U/kg

Subsequent: 50 U/kg every 24 hours


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von Willebrand Disease


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von Willebrand factor: Carrier of factor VIIIAnchors platelets to subendothelium

Bridge between platelets

Inheritance Autosomal dominant (tipe 1 and 2)Autosomal recessive (tipe 3)

Incidence 1/10,000

Majority of these people do not have

symptoms


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present with varying degrees ofbleeding tendency, usually in the formof easy bruising, nosebleeds andbleeding gums. Women mayexperience heavy menstrual periodsand blood loss during childbirth.
http://en.wikipedia.org/wiki/Bleeding_tendencyhttp://en.wikipedia.org/wiki/Epistaxishttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Childbirthhttp://en.wikipedia.org/wiki/Childbirthhttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Epistaxishttp://en.wikipedia.org/wiki/Bleeding_tendency


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Laboratory evaluation of von Willebranddisease

ClassificationType 1 Partial quantitative deficiency

Type 2 Qualitative deficiency

Type 3 Total quantitative deficiency

Diagnostic tests:von Willebrand type

Assay 1 2 3

vWF antigen


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Treatment of von Willebrand diseaseVaries by Classification

CryoprecipitateSource of fibrinogen, factor VIII and VWF

Only plasma fraction that consistently contains VWFmultimers

Correction of bleeding time is variable

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

endothelium

Duration of response is variable

Used for type 1 disease

Dosage 0.3 g/kg q 12 hr IV

Factor VIII concentrate (Humate-P) Virally inactivated product


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Bleeding disorder of Sistemicdisease


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Liver Disease

Decreased synthesis ofII, VII, IX, X, XI, and fibrinogenProlongation of PT, aPTT and Thrombin Time

Treatment

Fresh-frozen plasma infusion (immediate but temporaryeffect)

Vitamin K (usually ineffective)


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Vitamin K deficiency

Source of vitamin K Green vegetablesSynthesized by intestinal flora

Required for synthesis Factors II, VII, IX ,XProtein C and S

Causes of deficiency MalnutritionBiliary obstruction

Malabsorption Antibiotic therapy

Treatment Vitamin KFresh frozen plasma


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Coagulation cascade

Vitamin K dependant factors

XIIa

IIa

Intrinsic system (surface contact)

XII

XI XIa

Tissue factor

IX IXa VIIa VII

VIII VIIIa

Extrinsic system (tissue damage)

X

V Va

II

Fibrinogen Fibrin

(Thrombin)IIa

Xa

Vit i K d fi i d t f i


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Vitamin K deficiency due to warfarinoverdoseManaging high INR values

Clinical situation Guidelines

INR therapeutic, < 5 Lower or omit next dose;Resume therapy when INR is therapeutic

INR 5-9; no bleeding Lower or omit next dose;Resume therapy when INR is therapeutic

Omit dose and give vitamin K (1-2.5mg po)

Rapid reversal: vitamin K 2-4 mg po (repeat)

INR >9; no bleeding Omit dose; vitamin K 3-5 mg po; repeat asnecessary

Resume therapy at lower dose when INR therapeuticChest 2001:119;22-38s(supplement)

Vit i K d fi i d t f i


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Vitamin K deficiency due to warfarinoverdoseManaging high INR values in bleeding patients

Clinical situation Guidelines

INR > 20; serious bleeding Omit warfarinAny life-threatening bleeding Vitamin K 10 mg slow IV infusion

FFP factor rhVIIa (depending on urgency)

Repeat vitamin K injections every 12 hrs as needed

Disseminated Intravascular Coagulation


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Disseminated Intravascular Coagulation(DIC)Mechanism

Depletion of plateletsand coagulation factors

Systemic activationof coagulation

Thrombosis of smalland midsize vessels

with organ failure

Bleeding

Intravasculardeposition of fibrin


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Common clinical conditionsassociated with DIC

Sepsis

Trauma

Head injury

Fat embolism

Malignancy

Obstetrical complications

Amniotic fluid embolism Abruptio placentae

Vascular disorders

Reaction to toxin (e.g. snakevenom, drugs)

Immunologic disorders Severe allergic reaction

Transplant rejection


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DICTreatment approaches

Treatment of underlying disorder

Anticoagulation with heparin

Platelet transfusion

Fresh frozen plasma


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Objectives




i f bl di i


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Sites of bleeding inthrombocytopeniaSkin and mucous membranes

PetechiaeEcchymosisHemorrhagic vesiclesGingival bleeding and epistaxis

MenorrhagiaGastrointestinal bleeding

Intracranial bleeding


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Petechiae

Do not blanch with pressure(> < angiomas)

Not palpable(> < vasculitis)


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Classification of platelet disorders

Quantitativedisorders

Abnormal distribution

Dilution effectDecreased production

Increased destruction

Qualitative disorders

Inherited disorders (rare)

Acquired disorders

MedicationsChronic renal failure


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Acquired thrombocytopenia withshortened platelet survival

Associated withbleeding

Immune-mediatedthrombocytopenia(ITP)

Most drug-inducedthrombocytopenias

Most others

Associated withthrombosis

Thromboticthrombocytopenic purpura

DIC

Heparin-associatedthrombocytopenia

h h h b i


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Approach to the thrombocytopenicpatient

History Is the patient bleeding?

Are there symptoms of a secondary illness? (neoplasm, infectionautoimmune disease)

Is there a history of medications, alcohol use, or recenttransfusion?

Are there risk factors for HIV infection? Is there a family history of thrombocytopenia?

Do the sites of bleeding suggest a platelet defect?

Assess the number and function of platelets

CBC with peripheral smear Platelet function study

Platelet transfusions -


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Platelet transfusions complicationsTransfusion reactions

Higher incidence than in RBC transfusions Related to length of storage

Bacterial contamination

Platelet transfusion refractoriness

Alloimmune destruction of platelets (HLA antigens)Non-immune refractoriness

Microangiopathic hemolytic anemiaCoagulopathySplenic sequestrationFever and infection

Medications (Amphotericin, vancomycin, ATG, Interferons)


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Kebutuhan transfusi trombosit

Penyebabtrombositopenia

Derajattrombositopenia

Penyakit Penyerta

Fungsi trombosit

Jenis operasi.Transfusi akan mampu bertahan empat hari

Transfusi trombosit konsentrat pada ITPsebaiknya dihindari


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Objectives




Adj ncti e dr g therap for


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Adjunctive drug therapy forbleeding

Fresh frozen plasma Cryoprecipitate Epsilon-amino-caproic acid (Amicar)

DDAVP Recombinant human factor VIIa(Novoseven)


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Fresh frozen plasma

Content - plasma (decreased factor V and VIII)

Indications

Multiple coagulation deficiencies (liver disease, trauma)

DIC

Warfarin reversal

Coagulation deficiency (factor XI or VII)

Dose (225 ml/unit) 10-15 ml/kg

Note Viral screened product

ABO compatible

Cryoprecipitate


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Cryoprecipitate

Prepared from FFP

ContentFactor VIII, von Willebrand factor, fibrinogen

IndicationsFibrinogen deficiency

Uremiavon Willebrand disease

Dose (1 unit = 1 bag)1-2 units/10 kg body weight

A i i id (A i )


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Aminocaproic acid (Amicar)

Mechanism

Prevent activation plaminogen -> plasmin

Dose 50mg/kg po or IV q 4 hr

Uses

Primary menorrhagia Oral bleeding

Bleeding in patients with thrombocytopenia

Blood loss during cardiac surgery

Side effects GI toxicity

Thrombi formation

D i (DDAVP)


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Desmopressin (DDAVP)

Mechanism

Increased release of VWF from endothelium

Dose 0.3g/kg IV q12 hrs

150mg intranasal q12hrs

Uses Most patients with von Willebrand disease

Mild hemophilia A

Side effects

Facial flushing and headache Water retention and hyponatremia


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Tranexamic acid (Kalnex)

MECHANISM OF ACTION Forms areversible complex that displacesplasminogen from fibrin resulting ininhibition of fibrinolysis; it also inhibits the

proteolytic activity of plasmin

Hemophilia patient:

during and following tooth extraction:I.V.: 10 mg/kg immediately before surgery,

then 25 mg/kg/dose orally 3-4 times/day for

Recombinant human factor VIIa


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Recombinant human factor VIIa(rhVIIa; Novoseven)

Mechanism

Activates coagulation system through extrinsicpathway

Approved UseFactor VIII inhibitors in hemophiliacs

Dose: (1.2 mg/vial)

90 g/kg q 2 hrAdjust as clinically indicated


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Summary

Identify and correct any specific defect ofhemostasis

Use non-transfusional drugs wheneverpossible

RBC or blood component transfusion forsurgical procedures or large blood loss

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