basics of hemostasis christiane thienelt, md assistant professor of medicine hematology/oncology...

Basics of hemostasis

Christiane Thienelt, MD

Assistant Professor of Medicine

Hematology/Oncology

DVAMC/UC Denver

2014

Objectives

1. Overview of coagulation 2. Basic coagulation tests 3. Bleeding disorders

What is Hemostasis? Hemostasis=injury to blood vessel triggers a

series of reactions Formation of fibrin-platelets plugs Bleeding stops

1. vascular phase 2. platelet phase (primary hemostasis) 3. coagulation phase (secondary hemostasis) 4. Regulation of extension of clot by coagulation

factor inhibitors and by Fibrinolysis 5. remodeling and repair after arrest of bleeding

Hemostasis

Platelet plug forms=primary hemostasis

Stabilization by fibrin formation(clotting cascade)=secondary hemostasis

Extension of clotlimited by:

Natural anticoagulants

Fibrinolysis

What is Thrombosis?

Uncontrolled pathological clotting Propagation of a clot to occlude

normal blood flow Ironically, the generation of a

NORMAL hemostatic plug and the formation of an ABNORMAL thrombus are basically the same mechanisms!

Importance of Coagulation in Medicine

Good hemostasis=Good Surgery

Clot Busting ( Thrombolysis)= Cardiovascular Medicine, life-threatening PE ( pulmonary embolism)

Components of hemostasis

1. Endothelium-vessel wall 2. Platelets 3. Coagulation factors

Vessel Wall

Normal Endothelium: -inhibits coagulation -prevents platelet aggregation -promotes clot breakdown -provides barrier to reactive

elements in the vessel wall

Vessel WallPrevent blood from leaking out holes

in blood vessels

Vascular phase-Vessel Wall injury

Injury of blood vessel leads to VASOCONSTRICTION diverting

blood flow Collagen, Tissue factor and von

Willebrand factor (vWF) are exposed Platelet adhere, aggregate and

activate blood coagulation

Platelet Phase: Physiology

Megakaryocyte in bone marrow: precursor for platelets derived from hematopoietic stem cellsUp to 2000 plateletsBud off, circulate 7-10 daysSpleen: 1/3 of plateletsTPO: thrombopoietin main growth and maturation factor for megakaryocytes

Platelet adhesion: Blood Flow

From: Mechanisms in Hematology

Formation of a Platelet Plug

There are 4 events in the formation of a platelet plug:

Platelet adhesionPlatelet activationPlatelet aggregationFibrin formation and support of local coagulation

Smooth discoid shape of resting platelets

Spiny spheric shape of activated platelets


Lack /dysfunction of vWF=von Willebrand Factoris von Willebrand disease

Platelet Adhesion: Main mechanisms

=Platelets adhere to the injured surface and build a temporary clot (primary hemostasis)

Exposed platelets change shape (pseudopods)

Temporary bond between GPIb and vWF

Stimulated platelets expose membrane glycoproteins IIb and IIIa

IIb and IIIa bind fibrinogen and vWF

more platelets are recruited and aggregated

Platelet Adhesion

Binding of GPIIbIIIa to 1. subendothelial vWF secures stable platelet

adhesion to the vessel wall while its

2. binding to fibrinogen facilitates platelet Aggregation

Platelet Aggregation

Aggregation:Platelets are laced together through fibrinogen bridgesLocally thrombin converts the fibrinogen to fibrin stabilizing the platelet plug

Platelet Activation

Ligand-Receptor interactions Leads to intracellular signalling Exposure of GpIIb/IIIa

Release of dense and alpha granules

Platelet AGONISTSCalciumSerotoninADP/ATPThromboxane A2

vWF, fibrinogen, clotting factors Anticoagulants (protein S)Anti-heparins ( PF4)

Platelet Activation

New platelets stick to activated platelets and are themselves activated through release of compounds that further amplify platelet activation

These include (a) Products of oxidation of arachidonic

acid by the cyclooxygenase pathway that includes thromboxane A2 (this pathway is blocked by aspirin=Cox 1 inhibitor)***

(b) ADP released from dense granules


-Resultant intracellular signaling events lead to platelet activation -Binding of GPIIbIIIa to subendothelial vWF secures stable platelet adhesion to the vessel wall while its binding to fibrinogen facilitates platelet aggregation

Summary of Platelet Plug Formation

Adhesion Platelets adhere to damaged vessel wall directly via collagen

or indirectly via von Willebrand factor

Activation Excitatory agonists (collagen, thromboxane A2, etc) cause a

conformational change in platelet to expose Glycoprotein IIbIIIa binding sites for fibrinogen

Aggregation Platelets are laced together through fibrinogen bridges

Fibrin formation Locally thrombin converts the fibrinogen to fibrin stabilizing

the platelet plug

Platelet Plug-primary hemostasis

Platelet plug forms

Prevention of Bleeding:

Scaffold for secondary hemostasis

Coagulation phase: Clotting factors

Through two different pathways, the clotting cascade is activated and fibrinogen is converted into fibrin

Secondary hemostasis

Coagulation Phase

Clotting factors fill in gaps(clotting cascade makes fibrin,

the “glue” of a clot)

Prevention of Bleeding:

Clotting factors

Usually referred to by number (except prothrombin and fibrinogen)

Numbers written as Roman numerals

13 known procoagulants

Coagulation Cascade

Series of enzymatic reactions Activated when collagen, tissue

factor or negatively charged surfaces are exposed

Key reaction: production of thrombin Thrombin converts fibrinogen to

fibrin

THE CLOTTING MECHANISM

INTRINSIC EXTRINSIC

PROTHROMBIN THROMBIN

FIBRINOGEN

FIBRIN(II) (IIa)

(I) V

X

Tissue ThromboplastinCollagen

VII

XII

XI

IX

VIII

COMMON PATHWAY

Hemophilia B

Hemophilia A

Common Pathway

Xa with V, Calcium and phospholipid convert prothrombin (II) to thrombin (IIa)

“Prothrombinase complex” occurs on platelet surface

Thrombin has many substrates both procoagulant ( positive feedback loop) and anticoagulant ( negative feedback)


INTRINSIC EXTRINSIC


FIBRINOGEN

FIBRIN (clot)(II) (IIa)

(I)V

X

Tissue Thromboplastin=

Tissue Factor (TF)

Collagen

VII

XII

XI

IXVIII

Extrinsic Pathway

Precipitating event is exposure of tissue factor to blood

Tissue factor is a membrane protein which acts as cofactor for VIIa

Phospholipid, tissue factor and VIIa cleaves X Xa

Intrinsic System

Independent of VII

Contact activation of XII activates XI=contact to negatively charged surfaces

(kaolin, celite, silica) XIa activates IX

IXa with VIII can activate X


INTRINSIC EXTRINSIC


FIBRINOGEN

FIBRIN (=clot)(II) (IIa)

(I)V

X


VII

XII

XI

IXVIII

Formation of a Fibrin Clot-last step

Thrombin binds to fibrinogen and liberates fibrinopeptides A and B

Fibrin monomers form polymers by overlapping and interact laterally to form fibrin strands and sheets

Factor XIII cross links fibrin for a stable clot

Role of Vitamin K Factors II, VII, IX and X undergo vitamin K dependent gamma carboxylation

Reaction occurs in the liver

The anticoagulants protein C and S also are carboxylated

Fibrinogen FibrinThrombin


Prothrombin

XaVa


Prothrombin

XaVa

VIIa

TF

Extrinsic Pathway


Prothrombin

XaVa

VIIa

TF

Extrinsic Pathway

IXa

VIIIa

XIa

XIIa

Intrinsic pathway


Prothrombin

XaVa

VIIa

TF

Extrinsic Pathway

IXa

VIIIa

XIa

XIIa

Intrinsic pathway

XIIIa

Soft clot

FibrinHard clot


Prothrombin

XaVa

VIIa

TF

Extrinsic Pathway

IXa

VIIIa

XIa

XIIa

Intrinsic pathway

XIIIa

Soft clot

FibrinHard clot

VVIII

++

+

Control of Coagulation Normal balance towards

anticoagulation

Fibrinolysis=clot breakdown

Antithrombin III=natural anticoagulant

Proteins C and S=natural anticoagulants

Natural Anticoagulants: AT III, protein C, S

TFPI TF+ VIIa

IX+VIII

X+V

II +

Fibrinolysis CLOT

Antithrombin

Protein C and

Protein S

Heparin

Degradation of Factors V, VIII

Thrombin

Natural Anti-Coagulants

Natural anti-clotting factors(Protein C, Protein S, Antithrombin)

Spreading clot beyond where it is needed- limited by “anti-clotting” factors

Fibrinolysis

Clot breakdown system(fibrinolysis)

Extra clot and old clot “cleaned-up”by factors that “chew up” clot

Fibrin Fibrin Split Products (FSP)Plasmin

Fibrinolysis

Fibrinolytic phase

Lysis (=breakdown) of clot allows repair of vessel wall/tissue injury and normalizes flow through vessel

Fibrin is degraded by plasmin Plasmin originated from

plasminogen Plasminogen is activated by tissue

plasminogen activator (TPA) Fibrinolysis is inhibited by

plasminogen activator inhibitors and alpha2-antiplasmin

Fibrin Fibrin Split Products (FSP)D-Dimer

Plasmin

Plasminogen

tPA

Fibrinolysis

INHIBITORS of PLASMINOGENPlasminogen activator inhibitor (PAI-1) inhibits PlasminogenAlpha 2 antiplasmin

Commonly Used Pharmacologic Agents in

BleedingHemostatictranexamic acid (Cyklokapron):

5% mouthwash for prolonged bleeding in dentistry, antifibrinolytic

aminocaproic acid (Amikar): inhibits plasmin, antifibrinolytic, oral rinse, iv or tablets

Aprotonin(Trasylol), antifibrinolytic, withdrawn from Market

Activated factor VII, recombinant, bypasses intrinsic system

Summary Hemostasis

Depends on -vessel wall integrity -adequate platelet number -adequate Platelet function -adequate factor levels -adequate fibrinolysis

Objectives


Basic coagulation tests

1. Platelet count 2. Bleeding Time/Platelet function

testing 3. Prothrombin time (PT)/INR 4. aPTT (activated partial

Thromboplastin time) 5. Thrombin Time (TT) 6. Factor assay 7. D-Dimer

SEVERITY OF THROMBOCYTOPENIA

Normal >150,000/mm3

Mild 90-150,000/mm3

Moderate 20-90,000/mm3

Severe 5-20,000/mm3

Very Severe <5,000/mm3

Thrombocytopenia (=low platelet count)

Normal platelet count between 150,000-400,000/ul

Platelets 20–50,000: may see spontaneous hemorrhage and increased risk of hemorrhage with trauma or surgery So safe platelet count for surgery is

generally 50,000 or higher Platelets <10,000-20,000: can see

life-threatening spontaneous hemorrhage

Copyright ©2008 American Society of Hematology. Copyright restrictions may apply.

Maslak, P. ASH Image Bank 2008;2008:8-00089

Figure 1. This picture demonstrates petechiae in dependent areas of a thrombocytopenic patient with AML

Bleeding Time/Platelet function analyzer

Bleeding time measures platelet function, vessel wall and skin integrity

A template device makes a cut on the forearm and time to clot (2-9 minutes) is measured

Platelet function analyzer (PFA) can determine an in vitro bleeding time with agonists

Bleeding time

Old test to screen for vW Disease or other platelet function disorder Operator dependent, not

reproducible Elevated in patients with uremia and

liver disease-little prognostic value Also prolonged in patients taking

ASA or NSAIDS Does not correlate with bleeding

complications Not helpful-please do not order!

Platelet function screen Replaces the

bleeding time as a test of platelet function

PFA-100; ordered as “platelet function screen”

Blue top tube

Measures the time it takes for blood to block membrane coated with platelet agonists ( either collagen/epinephrine or collagen/ADP)

Prothrombin time (PT) Measures extrinsic pathway Useful for measurement of VII, X, V and II

and fibrinogen Calcium and thromboplastin (extract of

tissue) added to citrated plasma and time to clotting is measured in seconds

PT is sensitive to decreased levels of Vitamin K-dependent factors (exception factor IX), useful for monitoring oral anticoagulants (WARAFRIN)

Test results expressed in seconds


INTRINSIC EXTRINSIC


FIBRINOGEN

FIBRIN(II) (III)

(I)V

X


VII

XII

XI

IXVIII

Measured by PT

INR

For monitoring oral anticoagulants (warfarin, coumadin) expressed as INR (International Normalized Ratio)

Devised to correct for variations in instrumentations and reagents ( tissue thromboplastin)

Normal INR is 1.0 Therapeutic anticoagulation is 2-3

( for A fib, DVT, PE), occasionally 2.5-3.5 ( for artificial valves)

INR equation

[Patient PT/Mean Normal PT]ISI=INR

ISI=international sensitivity indexINR=international normalized ratio


INTRINSIC EXTRINSIC


FIBRINOGEN

FIBRIN(II) (III)

(I)V

X


VII

XII

XI

IXVIII

Measured by PTT

Activated Partial thromboplastin time (aPTT) Measures the intrinsic pathway Surface activating agent and

phospholipid is added to citrated plasma

Activated plasma is then recalcified and time to clotting measured in seconds

aPTT

Measures the activity of the entire clotting pathway except Factor VII ( because Factor VII is extrinsic pathway)

Useful to detect Factor VIII, IX, XI, XII deficiencies

Sensitive to inhibition by heparin and fibrin split products




Thromboplastin time) 5. Thrombin Time (TT) 6. Factor assay 7. D-Dimer 8. Bleeding Time/Platelet function

testing

Thrombin Time

Excess thrombin is added to plasma Measure the rate of conversion of

fibrinogen to fibrin upon the addition of thrombin to plasma

Prolonged in the presence of heparin, low or abnormal fibrinogen and fibrinogen/fibrin degradation products


INTRINSIC EXTRINSIC


FIBRINOGEN

FIBRIN(II) (III)

(I)V

X


VII

XII

XI

IXVIII

COMMON PATHWAY

Factor assay

Each of the factors is individually assayed using modifications of the PT or PTT test

Pooled normal plasma is defined as 100% activity

Factor levels vary tremendously from person to person ( normal is 50-150 % activity)


Prothrombin

XaVa

VIIa

TF

Extrinsic Pathway

IXa

VIIIa

XIa

XIIa

Intrinsic pathway

XIIIa

Soft clot

FibrinHard clot

VVIII

++

+

D-Dimer

Fibrin monomer bind to form thrombus

Factor XIII binds their D-domains together

Fibrinolysis: Degradation fragment is called D-Dimer

D-Dimer is a fibrin split product

D-Dimer

Elevated D-Dimer levels indicate that

1) Thrombin has acted on fibrinogen to form a fibrin monomer which bonded to another monomer aided by Factor XIII

2) clot was lysed by plasmin (=fibrinolysis)

Objectives


Evaluation of Bleeding

Patients may consider an appropriate amount of bruising or bleeding to be excessive

Therefore, a detailed history is essential in the workup

Approach to the bleeding patient-

History is the most important tool 1. Have you ever had a nosebleed? How frequent did these

occur? Did it require a trip to the hospital? 2. Have you ever had dental work? Did it require stitching

or packing due to the bleeding? Did it bleed the next day? 3. What surgeries have you undergone? Did any of them

require transfusions? Did your surgeon comment on excessive bleeding?

4. What is the biggest bruise you ever had? How did it happen?

5. How long are your menstrual periods? Have you ever been so anemic you needed to be on iron replacement? Did you have excessive bleeding after childbirth or require a transfusion then?

6. Have you ever had bleeding when you urinated, from your stomach or from your gastrointestinal tract?

7. Do you bleed when you brush your teeth?From Hemostasis and Thrombosis; 1999Landes Bioscience

Approach to the bleeding patient

1. History/Severity of symptoms: Major vs. Minor bleeding, menorrhagia, bruising, nosebleeds (Acquired vs. inherited)

2. Prior stressors (contact sports, trauma, broken bones, surgeries, pregnancies)

3. Family History (extended, especially males) 4. Drugs (Rx plus OTC) 5. Previous coagulation parameters available? (PT, PTT,

platelet count) 6. Concurrent illnesses

Case A 40 y/o woman presents to your office for dental evaluation. She

will need extraction of several teeth. Years ago, she had wisdom teeth extraction performed and tells you that she started to bleed about 4 hrs after extraction and needed plasma transfusion to stop the bleeding. She is very apprehensive about any further extractions. You order the following labs:

CBC shows normal platelets count at 267. PT is normal at 12.3 sec, PTT is normal at 28 sec. INR is 1.0. Platelet function testing is normal.

She also tells you that she bled each time after her deliveries ( she has 4 children) where she lost enough blood to receive blood transfusions each time. She bled after her gallbladder surgery and her tonsillectomy.

You tell her:A) based on her history, she must have a bleeding disorderB) you don’t think, she has a bleeding disorder because all of her

testing has been normalC) you think, she must have had an incompetent surgeon/dentist

before and YOU will be more carefulD) you think, she needs more testing

Bleeding disorders

Inherited bleeding disorders

Von Willebrands disease

Hemophilia A and B

Other factor deficiencies

Acquired bleeding disorders

Thrombocytopenia Liver disease Vitamin K

deficiency/warfarin overdose

DIC Renal

disease/uremia Drug induced (ASA)

Bleeding disorders

1. Vessel defects 2. Platelet disorders 3. Coagulation abnormalities 4. Other

Vessel defects

1. Vitamin C deficiency 2. Bacterial/viral infections 3. Rheumatologic disorders

(vasculitis)

Vessel wall integrity

Peri-follicular hemorrhage

Scorbutic gingivitis

Bleeding disorders


Platelet disorders

Thrombocytopenia ( decreased numbers of platelets)

Platelet function defects ( abnormal platelet function)

Thrombocytopenia (=low platelet count)

Normal platelet count between 150,000-400,000/ul

Platelets 20–50,000: may see spontaneous hemorrhage and increased risk of hemorrhage with trauma or surgery So safe platelet count for surgery is

generally 50,000 or higher Platelets <10,000-20,000: can see

life-threatening spontaneous hemorrhage

Causes of Thrombocytopenia

Caused by either of these mechanisms:Decreased production of platelets

Increased destruction of platelets

Distribution/Dilution disorders (Increased sequestration of platelets due to splenomegaly)

Petechiae

Do not blanch with pressure

Not palpable

Impaired/Decreased Platelet production

Bone marrow failure -nutritional deficiencies ( Vitamin B12, Folate) -ETOH -malignancies ( leukemia, lymphoma, metastatic

disease to bone marrow, myelodysplastic syndrome)

-Drug-induced (chemotherapy , antibiotics, thiazide diuretics etc)

-Radiation ( marrow in Radiation field) -Viral infections (HIV, Hep C) -congenital

Disorders causing Increased Destruction of

Platelets Thrombocytopenia occurs when platelets are rapidly destroyed and bone marrow cannot compensate

Most common cause is immune thrombocytopenia where platelets are coated with anti-platelet antibodies leading to premature removal of platelets by the spleen

Disorders: Immune thrombocytopenia (ITP) – common

cause (outpatient) DIC – rare cause (usually inpatient setting) Sepsis – rare cause (inpatient) Thrombotic thrombocytopenic purpura (TTP) –

rare cause, inpatients

Thrombocytopenia

ITP ( immune thrombocytopenic purpura)

Autoimmune disorder caused by antibodies that lead to destruction of platelets

Disorders of dilution/distribution

Active bleeding or clotting (consumption)

Massive transfusion (dilution) Hypersplenism ( sequestration of

platelets in enlarged spleen)-normally 30% of platelets stored in spleen-with increase in size, more platelets get

sequestered in spleen-most often seen in Liver disease ( Liver cirrhsois)-

>portal hypertension->splenomegaly

Abnormal platelet function (platelet number normal) 1. Drug induced ( aspirin, NSAIDs,

Plavix) -stop aspirin 5-7 days before elective

surgery 2. uremia 3. congenital platelet function

defects(Glanzman thrombasthenia, Bernard-

Soulier syndrome-missing platelet receptor proteins)

Bleeding disorders


Hemophilia

• X-linked deficiency of Factor VIII (hemophilia A) or Factor IX (hemophilia B)

• Males primarily affected• Carrier females can be symptomatic• Elevated PTT is only abnormal

screening test

Hemophilia A and B

Hemophilia A – Factor VIII deficiency 1:5000 male births

Hemophilia B – Factor IX deficiency 1:50,000 male births

Many new mutations; negative family history does not rule out hemophilia

Diagnosis of Hemophilia Screen males with unexplained

hematomas, bruises and post surgical or traumatic bleeding

PTT ranges from high normal to very prolonged

Assay Factor activity to distinguish Hemophilia A and B-important for treatment

Hemophilia-Clinical manifestations

Clinical manifestations (hemophilia A & B indistinguishable)

Hemarthrosis (most common)Fixed joints

Soft tissue hematomas (e.g., muscle)Muscle atrophyShortened tendons

Other sites of bleedingUrinary tractCNS, neck (may be life-threatening)

Prolonged bleeding after surgery or dental extractions

Ecchymoses

(typical of coagulation factor disorders)

Coagulation Factor Testing

Pooled normal plasma is defined as 100% activity

Normals are ~50-150% activity Severe hemophilia - <1% - spontaneous

bleeds Moderate 2-5%-bleed with minor

trauma Mild hemophilia 5-10% - bleed with

severe trauma, surgery and dental procedures

Factor Level does not change significantly throughout life!

Factor XI Deficiency

PTT prolonged

Post-operative bleeding

Variable bleeding history

Autosomal recessive

Variable incidence in populations

Hemophilia

Hemophilia A

Hemophilia B

Factor XI deficiency

Affected Coagulation factor

F VIII F IX F XI

Inheritance

X linked recessive

X linked recessive

Autosomal recessive

Incidence 1/5,000 males

1/50,000males

Ashkenazi Jews (5% of population

Treatment of hemophilia A:

Factor VIII concentrates Preferred agent: recombinant goal range : 30-40% factor level hemorrhagic joints 100% factor level in patients undergoing major surgery or

CNS trauma infuse as fast as possible 1 unit of factor VIII raises plasma level by 2%

(Desired Factor VIII concentration x weight in kg

2

Bleeding disorders


Von Willebrand Disease

Most common congenital bleeding disorder

Autosomal dominant Abnormality in platelet/endothelial

interaction Clinical problems:

Mucosal bleeding Nose bleeds GI bleeds Menorrhagia Bleeding after surgery if no correction

Von Willebrand Disease:

Pathophysiology Von Willebrand’s protein is extremely large

protein in a series of forms with 2 functions

1ST FUNCTION: Adheres platelets to exposed collagen at the

site of a wound or vessel disruption

2nd FUNCTION: Carry Factor VIII Without this protein, Factor VIII has a VERY

short half-life

Von Willebrand Disease: Diagnosis

(Initial) Tests for von Willebrand’s Disease: Factor VIII level normal or decreased

(measures 2nd function of vW protein)

von Willebrand’s antigen (measures amount of vW protein) < 0.30 IU/dL

von Willebrand’s activity, aka ristocetin cofactor activity (measures function of patient’s vW protein using donor platelets) < 0.30 IU/dL

Blood Type (Type 0) has lower baseline levels)

Von Willebrand Disease Types

Type 1: Partial quantitative vWF deficiency.

(70-80% cases) Type 2: Qualitative defects – abnormal

function of vW protein(15-30% cases) Type 3: Almost complete absence vWF

(Rare)

Von Willebrand Disease Treatment - DDAVP

Need to avoid aspirin, NSAID’s, other platelet inhibiting drugs

Long term prophylaxis rarely required DDAVP (arginine vasopressin) enhances

already synthesized vWF release from endothelial stores so effective in type 1 but not type 2 or type 3 disease

Once stores depleted, will need time to make more

vW factor DDAVP is available as nasal spray

(Stimate) or intravenous form Trial in a non-bleeding state is warranted

before elective procedure to verify pt will respond with increased levels

Von Willebrand Disease Treatment – vWF Replacement Therapy

“Intermediate purity” factor VIII (also rich in vWF) concentrates are most commonly used

Mainly used in type 2 and 3 disease Indications in type 1 disease:

More severe disease, especially when severe bleeding involved

When other measures have failed Post op setting when prolonged treatment

maybe needed, because DDAVP will not work repeteadly

Case 1

A 23 y/o woman is sent to you for wisdom teeth extraction. On pre-screening form, patient reports “very heavy menses” that have always been present. She works as a hair stylist and has to take off work for her periods. What should you do next?

A) inquire about previous surgeries/extractions, i.e. obtain a bleeding history

B) Proceed with extractions and see if she bleeds

C) Send for hematology evaluationD)Tell the patient that she has a bleeding

disorder and deny her surgery.

Case 2

The same patient tells you that she had a vaginal delivery 2 years ago and bled extensively about 8 days after her delivery. She required a Blood transfusion at that time. No obstetric reason for her bleeding was found. She was supposed to see a hematologist at that time but never followed up. What would be the best way to proceed now?

A) Obtain a hematology evaluation nowB) Assume, she has hemophilia and give a factor

concentrate before the extractionC) Assume, she has von Willebrand disease and

give DDAVPD) Assume, she has a platelet disorder and arrange

for transfusion of platelets before her extraction.

Case 3

The same patient is seen by hematology and is diagnosed with von Willebrand disease, Type I, the most common type. The hematologist most likely will recommend:

A) 1 dose of DDAVP i.v. before extraction

B) 1 dose of Humate P (Factor VIII)C) Transfusion of platelets before

extractionD) Cryoprecipitate before extraction

Case 4

In a patient with von Willebrand disease, which types of bleeding would you NOT expect?

A) nosebleedsB) excessive menstrual bleeding C) joint bleeds ( hemarthrosis)D) post-procedural bleeding

Case 5

The same patient eventually undergoes tooth extraction with appropriate pre-treatment and does well. She asks you whether her now 2 y/o son could have von Willebrand disease as well?

A) yes, please explain B) no, please explain

Bleeding History Pearls***

Mucocutaneous bleeding:Platelet or von Willebrand factor defect

Soft Tissue/Joint/Deep Bleeding:

Coagulopathy (Factor deficiency=Hemophilia)

Questions?

basics of hemostasis christiane thienelt, md assistant professor of medicine hematology/oncology...

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