Bleeding DisordersFor Surgeons

J. Bormanis

Bleeding disorders• What are the possibilities

• What questions have good yield

• What are screening tests

• What Lab tests are worrisome and what is the risk

Clinical Approach• When did it start ?

• Dental history

• Spontanous bruising

• Bleeding at surgery

• Bleeding into joints

• Menstrual bleeding

• Epistaxis

• One site only? Where ? When ?

High yield questions• Family history

• Pattern of bleeding - where

• Difficult to stop or

• Re-bleeds

• Drug history

• Alcohol intake

• Co Morbid disease

Physical Examination in Bleeding Disorders

• Check sites of bleeding• Is it local or generalized ?• what are the manifestations, petichiae,

ecchymoses, hematoma ?• Are there vessel wall abnormalities, telangectasia,

“palpable purpura, perifollicular hemorrhages” ?• Are there signs of a connective disease process• Are There signs of a systemic disease• The type of bleeding should give a good clue as to

which part of hemostasis is affected as well as the severity

Laboratory testing• History and physical

• Type of tests guided by clinical features

• Screening tests

• Further tests

• Definitive tests

Normal Hemostasis

Screening Tests• INR

Extrinsic pathway

• PTT (activated partial thromboplastin time)

intrinsic pathway

• Thrombin time

final pathway

• Platelet count

• Bleeding time – PFA (not useful)

Laboratory tests further testing• INR

• PTT

• TT thrombin time

• Factor assays

• Tests of fibrinolysis

• platelet count

• Bleeding time

• platelet function tests

• Special tests

Inerpretation of tests• If isolated abnormality likely a single defect

• eg PTT - possible hemophilia, vWd

• If unexplained do mixing test for inhibitor

• IF more than one abnormality then more complex

• eg. INR and PTT - vitamin K- Coumadin

• eg. PTT,TT heparin

• eg INR , PTT, TT, Platelets

• DIC or liver disease

Clinical Cases

Case 1• It is Friday at 4:40pm

• Lab calls

• Your patient is being preped for urgent surgery.

• INR 6.5

• What to do ?

Why INR’s go out of control

Vitamin K• Warfarin affects factors II,VII,IX and X

• These are the vitamin K dependent factors

• Can reverse warfarin effect

• Takes time

• Available forms ?

Efficacy of route of administration

Reversing INR wityh vitamin K• Depends on clinical scenario

• Complete reversal

• Partial reversal (too high INR)

• IV or oral forms prefered

• For complete reversal 5-10 mg IV q12h for 2 doses will reverse completely in 36-48 hours.

• 1-2 mg will decrease INR to therapeutic

• Level within 12-24 hrs

Current practice

Sent as 2 vials in a 50 cc mini bag to infuse at 3c/min

Case 2• You are on call for ENT and are asked to see an

18 year old girl with refractory nosebleed.• The nose is packed and bleeding does not stop.• You notice a few bruises• Blood sent off to lab.• The lab calls at 6:00 Pm with a “critical” platelet

count of 10

• What is likely diagnosis• What to do ?

ITP Immune thromboctopenic purpura

• What is needed for diagnosis

• Bone marrow examination

• Anti platelet antibodies

• When isolated and very low ITP is most likely diagnosis

• Could be a part of another disease but not likely (SLE , inf mono)

• Does it require hospitalization ?

ITP continued• If mucosal bleeding platelets are less than 6

• Needs action

• Steroids

• IVIG

• Anti D

• What about splenectomy

• New treatments

• Rituximab

• TPO agonists

Case3• A 48 year old woman appears in emerg

with jaundice of 3 weeks duration

• Exam – jaundice - some RUQ pain an palpation

• Blood tests

• CBC Hgb 125, WBC 7.6 Plat 345

• INR 2.6 ptt 42

• What is likely diagnosis

• What to Do ?

Vitamin K deficiency• Obstructive jaundice

• Malabsorption of Vit K dependent factors

• Older people at risk

• Post surgery at risk

• Treatment

• Oral or IV Vitamin K

Case 4• A 54 year old male comes to emerg feeling

unwell.

• Exam

• Mild jaundice, some telangectasis on skin

• Mod ascites.

• CBC - Hgb 110 WBC 2.5 plat 68

• INR 1.6 Ptt 41 TT 25

• What is likely diagnosis ?

Hepatic dysfunction - Cirrhosis• Liver makes and degrades

• Coagulation is affected by decreased production and impaired degradation of activated factors

• Chronic DIC

• Splenomegaly

• Trearment only if bleeding

• Liver transplant

Case 5• 18 year old male scheduled for

tonsillectomy

• History of easy bleeding

• Exam normal no bruises

• CBC normal

• INR 1.1 PTT 45

• What is likely diagnosis ?

• How to diagnose ?

Hemophilia• X linked bleeding disorders characterized by

spontaneous development of large hematomes in deep tissues.

• May lead to joint bleeding, or into other closed structures

• Joint cavity bleeding leads to deformed joints

• bleeding may be spontaneous or asssociated with mild or moderate injury

Hemophilia types• Hemophilia A

• absent or decreased factor VIII

• Hemophilia B• lack of factor IX• similar in symptoms to Hemophilia A

• Hemophilia A is 10 times more common than hemophilia B

Genetics of Factor VIII• Single chain polypeptide• Produced mainly in Liver

• remember linked to VWf

• Gene deletion - no factor VIII• Point mutation - abnormal factor VIII• Base deletion - Abnormal Factor VIII• Coded on X chromosome -therefore only males

affected (transmitted by female carriers)

Hemophilia types• Subclassified by level of factors

• Levels correspond to clinical symptoms

• Mild 5-30% factor activity

• Moderate 1-5% activity

• Severe <1% activity

Hemophilia - Clinical Picture• Mild- do not develop spontaneous bleeding, but

do bleed after injury or surgery• Many patients have sever disease• Joint Bleeding results in severe disability

• hemarthroses

• chronic arthritis

• muscle bleeds

• Social, economic,psychological problems

Case 6• 17 year old girl with mennorhagia

• History of easy bruising

• Possible history of easy bruising

• CBC normal

• INR 1.1 PTT 32 (2 sec prolonged)

• What is diagnosis

• How to diagnose ?

• Treatment ?

Von Willebrand’s Disease• Most frequent inherited bleeding disorder

• 1% - 1/100 of western population

• less severe than hemophilia

• Disease results from a decrease or absence of Von Willebrand factor for platelet adhesion

• Affects primary hemostasis

Von Willebrand’s Disease and Factor VIII

• VW factor produced in megakaryocytes and endothelial cells

• Coded on chromosome 12• Autosomal dominant inheritance• Large molecule, and multimeric• Monomers undergoglycolisation and

multimerization before secretion• Different multimer size = disease

Von Willebrand’s Disease and Factor

• VW is carrier for factor VIII

• Factor VIII-VWf complex

• Factor VIII protein carried in circulation as complex with VWf

• Reacts with platelet via GP Ib

• Therefore can be problems with platelets and factor VIII

Clinical features of Von Willebrand’s Disease

• Generally mild bleeding - often unrecognized until surgery or injury• epistaxis, menorrhagia, easy bruising, dental

and post operative bleeding

• Can be severe in certain types

• Requires accurate diagnosis

• Requires specific treatment

VW -types• Type I

• most frequent, quantitave defect (decreased VWf )

• Type II• qualitative defect (abnormal VWf )

• Type III• severe, rare, (absence of VWf )

How to diagnose Von Willebrands disease

• Clinical history

• Factor VIII level

• Bleeding time

• Measure VWf and perform aggregation tests

• Do gel electrophoresis for multimers

Anti platelet agents• ASA

• Not likely to create problems

• Safer to give if there for cardiovascular reasons

• Clopidogrel

• If elective stop before.

• Minimum 3 days

• More than 5 days likely unnecessary

Massive bleeding

What are the critical issues ?

Questions

Massive Transfusion Protocol

The Ottawa HospitalOttawa, Ontario