Coagulation Disorders 2 (CMPP)

Whta is the most common inhertied bleeding disorder

VWD

Von Willebrand Disease (VWD)

Mutation of the vWF gene

Result is either vWF deficiency or dysfunction

What chromosome contains vWF genes

Chromosome 12

How does VWD present

Often very mild

Epistaxis

Bruising

Mucocutanous Bleeding

Prlonged superficial cut bleeding

Heavy Menstral / Postpartum Bleeding

GI Bleeds

What are the types of VWD

Type 1

Type 2A

Type 2B

Type 2M

Type 2N

Type 3

Type 1 VWD

An autosomal dominant mutation that results in a decrease in vWF

What is the most common type of VWD

Type 1

Type 2A VWD

A mutation that Impaired ability to form multimers reducing GP1b bind

Type 2B VWD

A mutation that caauses High binding ability to GP1b, causing thrombocytopenia

Type 2M VWD

A mutation that causes Low ability to bind to GP1b

Type 2N VWD

A mutation that Reduces bindng to VIIIa

Type 3 VWD

rare autosomal recessive condition Result is absent or severely low vWF

What is the most severe form of VWD

Type 3

When do we work up a patient for VWD

•Increased Hx of bleeding

•+ FHx for vWD or “bleeding d/o”

•Mild unexplained thrombocytopenia

•Mild unexplained prolonged aPTT

•Dx of Hemophilia A in females

What is the initial workup + results for VWD

•CBC = Microcytic Anemia + Thrombocytopenia (Mainly 2B)

•aPTT = Mild prolongation

•PT / INR = Normal

What are the VWD specific tests

vWF antigen (vWF:Ag) for amount of vWF

vWF activity for function of vWF (Ristocetin cofactor)

VIII activity

vWF:Ag test

A test that determines the quanity of vWF in plasma

What can trend serum vWF to be lower

Type O Blood

Causcian

What are the results of vWF:Ag

< 30 % =vWD

30-50% = Low but miss criteria for vWD

> 50% =Normal

Risocetin

A former Abx that is used as a PTL activater

Ristocetin cofactor (RCoF) activity

A test that mixes ristocetin, poor PTL plasma, and fixed PTLs

Test for VWD

Ristocetin-Induced Platelet Aggregation Test (RIPA)

•the binding affinity of patient vWF to patient GP1b

What is cutoff on RCoF for VWD

agglutitation < 30 IU/dL

How does RIPA differ from RCoF

RIPA uses PTL rich plasma wherease RCoF uses PTL poor plasma

RIA uses a lower amount of ristocetin

What is the purpose of RIPA

: Identify vWD-2B

What are the results for VWD

•< 0.6 mg/mL of ristocetin = vWF normal

•In vWD-2B = Occurs at 0.4-0.5 mg/mL

What are specific test results for Type 1 VWD

vWF:Ag =Low

RCoF =Decreased

RIPA = Decreased

Multimer = Uniform decrease

What are specific test results for Type 2A VWD

vWF:Ag = Normal

RCoF =Decreased

RIPA = Decreased

Multimer = Large multimer decrease

What are specific test results for Type 2B VWD

•vWF:Ag = Normal

•RCoF =Decreased

•RIPA = Increased

•Multimer = Decrease large multimers

What are specific test results for Type 2M VWD

vWF:Ag = Normal

RCoF = Decrease

RIPA = Decrease

Multimer = Uniform decrease

What are specific test results for Type 2N VWD

vWF:Ag =Normal

RCoF =Normal

RIPA = Normal

Multimer = Normal

ONLY VIII DYSFUNCTION

What are specific test results for Type 3 VWD

•vWF:Ag = Absent / Severe Low

•RCoF = Marked decrease / absent

•RIPA = Marked decrease / absent

•Multimer = Undectable

What is tx for Type 1 VWD

•Start desmopressin

•Consider vWF concentrate

What is tx for Type 2A VWD

•Start desmopressin

•Consider vWF concentrate

What is tx for Type 2M VWD

•Start desmopressin

•Consider vWF concentrate

Desmopressin (DDAVP)

An intranasala drug that promotes release of vWF and VIII from endothelium

What are side effects of DDAVP

Facial Flushing + Headache + Hyponaterima

What is tx for Type 2B VWD

•Avoid desmopressin

•Use vWF concentrates

What is tx for Type 2N VWD

Start desmopressin

Consider VIII concentrare if not responding

What is tx for Type 3 VWD

vWF replacement therapy

VIII concentrate

Hemophilia

•x-linked bleeding disorders causing a factor deficinect

Hemophila A

•x-linked Factor VIII deficiency

Hemophilia B

•x-linked Factor IX deficiency

What disease is also called Christmas Disease

Hemophilia B

What is the tx for Hemophila

Factor transfusion

How can hemophilia in the infant present

•asymptomatic

Cephalohematoma

ICH (Possible spontaneous)

Heel Stick Bleed

Circumcision Site Bleed

Venipuncture Bleed

When is the common onset for hemophilia presentations

1 and ½ years

How does hemophilia present in children / adults

Easy Brusing

Forehead Hematoma

Hemarthrosis

Muscular Bleed

Immediate and Delayed Bleeds from Trauma and Surgery

Spontaneous Bleeding

Hemarthrosis

•painful and debilitating condition of the joints

Complication of hemophilia

How does hemarthrosis present?

Decreased limb use + Stiffness

Prodromal Warmth followed by Pain and Swelling

Can lead to joint destruction

How will initial labs for hemophilia present

CBC = Likely normal

PT/INR = Normal

aPTT = Prolonged

How will specific tests look for hemophilia

vWF:Ag = Normal

VIII assay = Decreased in Hem A (CHECK for VWD)

IX assay = Decreased in Hem B

Due to overlapping etiology, what two conditions can be mistaken for each other

Hemophilia A

Type 2N VWD

What are the result ranges for factor assay

Normal = 50-150%

Mild hemophila = 5-40%

Moderate hemophilia = 1-5%

Severe hemophilia = < 1 %

Who is part of the care time for hemophilia

•Hematologists + Nurse + Social Worker + PT

When giving a vaccine to hemophilia patients, what should be done

Ice/Pressure for 5 minutes after

Largest gauge

What should we encourage in hemophilia patients

Execrise

What medications should hemophilic patients avoid

ASA

NSAIDs

What can we give for hemophilia

DDAVP (Mild Hemophilia A)

Who commonly gets Vitamin K deficiency

Newborns (Reason for IM shot)

What are sources of Vitamin K

Green Veg

Gut Flora

What is needed to absorp Vitamin K

Pancreatic Enzymes

Bile Salts

What are risk factors Vitamin K deficiency

Malabsorption (Celiac / IBD / Post-Op)

Malnurition

Fat Malabsorption Sydnromes

Severe Liver Disease

CF

Primary Sclerosing Cholangitis

Recurrent Abx

How does Vitamin K deficiency present

Easy Bruise

Mucosal Bleed

Splinter Hemorrhage

Hematuria

Melena

How will labs appear with Vitamin K deficiency?

PT / INR = Prolonged

aPTT = Normal to Prolonged

Factor II, VII, IX, X = Decreased levels (< 50%)

PIVKA-II = Elevated (More sensitive than PT/INR)

How is Vitamin K deficiency treated

Vitamin K

How do we divide causes of VTE

Provoked Causes

Unprovoked Causes

Provoked VTE

Clotting that occurs due to a violation of Virchow’s Traid

Unprovoked VTE

Clots that are the result of hereditary conditions

What hereditary condition cause hypercoagulable state

Factor V Leiden

Prothrombin G20210A

Protein S deficiency

Protein C deficiency

ATIII deficiency

Factor V Leiden

A hypercoagulable inherited condition

F5 gene

A gene that codes for the cleavage site in Protein C

In Factor V Leiden, it is mutuated so that Protein cannot inactivate Va

how can Factor V Leiden present

•VTE

•DVT

•PE

•Recurrent late fetal loss

What is the workup for unprovked VTE

Look for S/S of malignancy

Order CBC + CMP + CXR

Do a hypercoagulable panel

Do cancer screening as appropriate

What are the parts of the hypercoagulable panel

Factor V (Leiden) Mutation

Prothrombin 20210G

Protein C activity

Protein S antigen

Antithrombin-heparin (AT) cofactor assay

Anti-beta2-glycoprotein-I antibodies (Anti-B2GPI)

Anticardiolipid Antibodies (aCL)

Lupus Anticoagulant (LA)

How long must anticoagulants be stopped before taking hypercoagulable panel

2 weeks

If doing hypercoaguable test during acute thrombosis, which parts of the panel is done?

DNA Test (Factor V and Prothrombin 20210G)

How is Factor V Leiden tx

•Hepburn Bridge to Coumadin (Warframe)

•DOACS

How long do we treat Factor V Leiden

•3 – 6 months

What is the most common hypercoagulable condition

Factor V Leiden

Prothrombin G20210A mutation

A mutation that makes prothrombin hyperfunctional

How can Prothrombin G20210A mutation present

VTE (x3 risk)
Recurrent DVT risk

How is Prothrombin G20210A mutation tx

•Heparin to Coumadin (INR= 2- 3)

•DOAC

•3- 6 month duration

Protein C deficiency

A rare inherited defecincy in Protein C

How does Protein C / S deficiency present

VTE seven times more likely than general population

Two thirds of patients develop spontaneous VTE

can appear as portal, hepatic, or mesenteric vein thrombosis

recurrent thrombosis is common

How is Protein C / S deficiency tx

DOAC for life

Warfarin-Induced Skin Necrosis

A rare complication to using warfarin therapy

When does Warfarin-Induced Skin Necrosis occur

First 10 days of dosing

How does Warfarin-Induced Skin Necrosis present

starts as a small erythematous macule

Purpura and skin necrosis will then appear due to occlusions

The area grows and becomes necrotic

mainly effects extremities, Breasts, trunk, and penis

Why does Protein C deficiency cause Warfarin-Induced Skin Necrosis

Warfarin causes a transient drop in Protein C and Protein S

How will Warfarin-Induced Skin Necrosis be tx

Stop warfarin

give Vitamin K and Protein C concentrate

Start heparin

Why do we bridge Coumadin with heparin

Coumadin takes a while for it to reach therapeutic values

When do we discontinue heparin during the bridge to Coumadin

INR > 2

Protein S deficiency

A inherited deficiency of Protein S

Antithrombin III Deficiency

A rare inherited defeicency of AT III

How does ATIII deficiency present?

Very high VTE risk, especially in pregnancy

50% get DVT by 50 (Unprovoked)

High recurrence rate

How is ATIII deficiency dx

Coag Labs = Normal

Suspect when a patient is heparin resistant (Fail to reach aPTT goals)

How is ATIII deficiency tx

Warfarin is preferred

DOAC can be used

AT concentrate can be given as an add-on or if anticoagulation is contraindicated

Tx is Lifelong

Antiphospholipid Syndrome

An autoimmunity against phospholipids, causing PTL to be attacked

What are the common antigens in Antiphospholipid Syndrome

Cardiolipid (aCL)

B2GPI