Hemostasis

Objectives

Biology of Hemostasis

Congenital Hemostasis Defects

Aquired Hemostasis Defects

Hypercoagulable States

Venous thromboembolism

Transfusion

Evaluation of the Surgical Patient at Hemostatic Risk

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Biology of Hemostasis
Complex process that prevents or terminates

blood loss from a disrupted intravascular space

Major physiologic events

Vascular constriction

Platelet plug formation

Fibrin formation

fibrinolysis

Biology of Hemostasis
Vascular Constriction

Initial vascular response to injury

Vasoconstriction linked to platelet plug formation

TXA2

ET

5-HT

Bradykinin & Fibrinopeptides

Biology of Hemostasis
Platelet Function

150-400K circulating platelets

~30% sequestered in the spleen

Thrombopeptin, IL-1, IL-6 mediate platelet

production

Biology of Hemostasis

Platelets play an integral

role in:

Formation of a
hemostatic plug

Contributes to thrombin
formation

Biology of Hemostasis
VC + platelet plug formation = PRIMARY

HEMOSTASIS

Reversible

Not associated with secretion

Biology of Hemostasis

Biology of Hemostasis

Intrinsic Pathway

All the components

leading to the fibrin clot
formation are intrinsic to
the circulating plasma

Elevated PTT associated

with an abnormality in
the intrinsic clotting
pathway

Biology of Hemostasis

Extrinsic Pathway

Requires exposure of
tissue factor on the
surface of the injured
vessel wall

Starts with Factor VII

Abnormality of the
extrinsic pathway is
associated with an
elevated PT

Biology of Hemostasis

Biology of Hemostasis

Fibrinolysis = lysis of the fibrin clot

Plasminogenplasmin by several activatorstPA, (kalikrein increases release of

tPA), uPA, factor XII

Plasminogen levels rise due to exercise, venous occlusion, and anoxia

Breakdown of the clot permits restoration of blood flow and fibrin clot in
vessel wall may be replaced with collagen

Binds and inhibits thrombin and factors IX, X, XI

Protein C

Antithrombin III

Plasminogen Plasmin degrades fibrin, Factor V and VIII

Vitamin K-dependent
Degrades fibrinogen and factors V and VIII

Protein S

Vitamin K-dependent
Protein C cofactor

Biology of Hemostasis
How do SCDs work?

The squeeze stimulates the release of tPA from

the endothelial cells of vessels. Induction of

fibrinolysis.

(tPA is selective for fibrin-bound plasminogen

and converts to plasmin; therefore, fibrinolysis
occurs mostly at the site of clot formation.)

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Congenital Hemostatic Defects

Coagulation Factor Deficiencies

Hemophilia

Factor VIII deficiency = Hemophilia A

Sex-linked recessive

Both prolonged aPTT and PT

Need level to be 100% pre-op and 30% post-op

Crosses placenta

Hemophiliac Joint

No aspiration; ice; ROM exercises, factor VIII

concentrate or cryoprecipitate
Factor IX deficiency = Hemophilia B/Christmas Disease

Sex-linked recessive

Need level 50% pre-operatively

Prolonged aPTT and normal PT

Tx-factor IX concentrate or cryoprecipitate

Congenital Hemostatic Defects

von Willibrands Disease

MOST COMMON congenital bleeding disorder

Low levels of vWFvariable decrease in Factor VIII due to
loss of the carrier protein
vWF is necessary for normal platelet aggregation; therefore
deficiency presents in a similar fashion to platelet disorders
Prolonged bleeding time, possible abnormal PTT, normal PT
Types

I-partial quantitative deficiency (AD)

II-qualitative defect (AD)
III-total deficiency (AR)

Txintermediate purity factor VIII or DDAVP (Type I or II

only)

Congenital Hemostatic
Defects
Platelet disorders

Glanzmanns thrombocytopeniadeficiency in
GIIbIIIa receptor of platelets; therefore, platelets
cannot bind to each other

Tx-platelets

Bernard SoulierGp1b receptor deficiency;

therefore, platelets cannot bind collagen via vWF

Tx-platelets

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Acquired Hemostatic
Defects

Anticoagulation

Heparinpotentiates ATIII action

Lovenoxpotentiates ATIII and inhibits both thrombin and

Factor Xa

Reversed with administration of protamine (1mg protamine

for every 100u heparin received)
Follow aPTTwant 1.5-2.5x upper limit of nl (60-90)
Does not cross placental barrier

more reliable therapeutic anticoagulation can be achieved

Drug effect can be determined by anti-Xa assay
No definitive reversal

Warfarin (Coumadin)

Inhibits Vitamin K synthesis

Reversed by FFP or Vitamin K administration
Follow INR/PT

Acquired Hemostatic
Defects
Why do we bridge with heparin or Lovenox

when initially starting Coumadin?

Protein C and S are inhibited before factors II,

VII, IX and X which makes the patient relatively

hypercoaguable for 5-7 days

Acquired Hemostatic
Defects
Antiplatelet Medications

AsprinPlatelet cyclooxygenase is irreversibly

inhibited ; decreases TXA2 which promotes
platelet aggregation

Plavix (Clopidogrel)ADP receptor antagonist

Pentoxifyllineinhibits platelet aggregation and

decreases viscosity of blood; used in treatment
of peripheral arterial disease

Acquired Hemostatic
Defects

Heparin Induced Thrombocytopenia

2/2 antiplatelet Ab (IgG) that results in platelet

destruction

Platelet count falls to <100K or by <50% in 5-7

days if first exposure or in 1-2 days if re-exposure

High incidence of platelet aggregation and

thrombosis (white clot)

If suspected

STOP heparin

Start alternate anticoagulation (lepirudin or

argatroban)

Acquired Hemostatic
Defects

Disseminated Intravascular Coagulation

Systemic process producing both thrombosis and

hemorrhage

Exposure of blood to procoagulants

Formation of fibrin in the circulation

Fibrinolysis

Depletion of clotting factors

end-organ damage

Dx= decreased platelets, prolonged PT and aPTT, low

fibrinogen, high fibrin split products, high D-dimer

Treat the underlying disease (sepsis, trauma, burns,

malignancy)

Acquired Hemostatic
Defects
Thrombocytopenia

MOST COMMON abnormality of hemostasis

Variety of etiologies (ITP, TTP, HUS, SLE,

lymphoma, secondary hypersplenism, portal
HTN, uremia)

In setting of massive transfusionexchange of

1L of blood volume (~11units) decreases
platelet count from 250K to 80K. Associated
impaired ADP-stimulated aggregation if >10units
of blood transfused.

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Hypercoagulable States
Factor V Leiden Deficiency

MOST COMMON congenital hypercoagulable

disorder

AD

Leiden variant of Factor V cannot be inactivated

by Protein C

Increased risk for DVT, spontaneous abortion

Tx = heparin or warfarin

Hypercoagulable States

AT-III deficiency

Spontaneous venous thrombosis

Heparin does not work on these patients unless
pretreated by FFP
Tx: AT-III concentrated

Antiphospholipid Antibody Syndrome

Presence of lupus anticoagulant that bind to

phospholipids and proteins on the cell membrane
an interfere with clotting; HOWEVER, associated
with thrombosis and habitual abortions (prolonged
PTT in the face of a hypercoagulable state)
Tx: Heparin, coumadin

Hypercoagulable States
Amicar

Aminocaproic acid

Inhibits fibrinolysis by inhibiting plasmin

Indications: DIC, persistent bleeding following

CPB, thrombolytic overdose

Aprotinin

Inhibits fibrinolysis by inhibiting activation of

plasminogen to plasmin

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Venous thromboembolism

DVT and PE

Virchows triad = stasis, endothelial injury,

hypercoagulability
Treatment for DVT

Greenfield filters

1st= warfarin x 6months

2nd= warfarin x 1year
3rd or significant PE = lifetime warfarin
For patients with contraindications to anticoagulation
Documented PE while on anticoagulation
Free-floating iliofemoral clot
IVC or femoral DVT
Patients who have undergone previous pulmonary embolectomy

PE most commonly caused by DVT in iliofemoral region

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Transfusion

PRBCs

1unit=~250mL
Storage life ~35days
1unit increases Hgb by 1 and Hct by 3
Fever without hemolysis is the most common
transfusion reaction (1 in 6,000)

Usually recipient antibody reaction against WBCs in

donor blood

Acute Hemolytic reactions occur 1 in 35,000

Caused by ABO incompatibility or Ab mediated usually

from human error (Ab in recipient binding to surface Ag
on donor RBC)
Sx=hypotension, fever, dyspnea, chest pain, low back
pain
Tx=fluids, diuretics, HCO3, histamine blockers, pressors

Transfusion

Platelets

50-100 billion in 50mL plasma

Can be stored for ~7 days (viability declines after 3
days)
Each platelet concentration should raise circulating
platelets by >5,000 (4-6 pack of platelets shound
increase platelets by 20-30K)
Febrile nonhemolytic reactions more common than
with PRBCs (incidence is ~30%)
Antiplatelet antibodies develop in 20% of patients
after 10-20 transfusions
Indictions in active bleeding: plt<50K or plt<100K in
setting of ICH; trauma victims who have received
multiple transfusion
Contraindicated in HIT and TTP

Transfusion

FFP
~250 mL collected from 1 unit whole blood by
apheresis
Stored between -18 and -30 degree C and is good
for 1 year
Dose is ~10-15mL/kg
Contains all coagulation factors, protein C, protein
S, and AT-III (only blood product with factor V)
Indications-warfarin overdose, liver failure,
dilutional coagulopathy associated with massive
transfusion
Highest risk of TRALIimportant to distinguish from
volume overload. Tx=supportive

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Evaluation of the Surgical

Patient at Hemostatic Risk

Preoperative Assessment

History

Bruises without apparent injury

Prolonged bleeding after injury
PMHxliver disease, congenital or acquired bleeding
disorders
Medications

LabsCBC, Coagulation panel, T&S or T&C

Intraoperative and Postoperative

Ineffective local hemostasis

Complications of blood transfusion
Consumptive coagulopathy
Fibrinolysis

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