J. Bormanis/ cg edits When did it start ? Dental history Spontanous bruising Bleeding at surgery...

COAGULATIONREVIEW

J. Bormanis/ cg edits

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

Approach to testing

History and physical Type of tests guided by

clinical features Screening tests Further tests Definitive tests

Normal Hemostasis

Blood Coagulation & Tests

Thrombin time

Screening Tests

Platelet count INR Extrinsic pathway PTT (activated partial thromboplastin

time) intrinsic pathway Thrombin time final pathway fibrinogen

Laboratory tests further testing

Factor assays Tests of fibrinolysis platelet function tests Special tests

Who is likely to bleed

Cirrhosis Renal dysfunction Age Drugs Right heart failure

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 (Cirrhosis) New anticoagulants

Dabigatran: TT, PTT Rivaroxaban: antiXa, PT/INR

PossibilitiesINR PTT TT PLAT Dx

2.4 43 16 396

1.3 65 >60 287

1.1 52 17 387

1.2 90 18 321

1.6 46 54 56

1.2 65 >60 24

1.4 41 >60 396

CLINICAL CASES

Case 1

It is Friday at 4:40pm Lab calls You are 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 (Vitamin K,

prothrombin complex concentrates)

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

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? 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 10

Needs action Steroids IVIG Anti D

splenectomy Newer 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 office 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

Treatment 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 hematomas 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 associated 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 severe 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% 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 Antigen and activity tests (Ristocetin

cofactor activity) Do gel electrophoresis for multimers

Anti platelet agents

ASA Not likelely to create problems Safer to give if there for cardivascular

reasons

Clopidogrel If elective stop before. Minimum 3 days More than 5 days unnecessary

Venous Thrombosis

common DVT, PE Splanchnic/portal vein thrombosis

Signs and Symptoms: Pain, swelling, erythema in an extremity SOB, CP, tachycardia, hypoxia

Diagnosis Clinical prediction models: Wells’ score D-dimer testing Imaging: US, CTPA, VQ Underlying risk factors

Thrombophilia: inherited, acquired

Venous Thrombosis

Treatment Low molecular weight heparin warfarin* IV unfractionated heparin warfarin

HIT (T): to consider if drop in platelet count in patient on a heparin agent

*continue LMWH for first 6 months after diagnosis of cancer associated VTE

New oral anticoagulant agents Rivaroxaban (Xarelto) Apixaban (Eliquis)

QUESTIONS