Chapter 110. Coagulation Disorders (Part 1) pot

Coagulation Disorders Part 1 Harrison's Internal Medicine > Chapter 110.. Coagulation Disorders Coagulation Disorders: Introduction Deficiencies of coagulation factors have been recog

Chapter 110 Coagulation Disorders

(Part 1)

Harrison's Internal Medicine > Chapter 110 Coagulation Disorders

Coagulation Disorders: Introduction

Deficiencies of coagulation factors have been recognized for centuries Patients with genetic deficiencies of plasma coagulation factors exhibit lifelong recurrent bleeding episodes into joints, muscles, and closed spaces, either spontaneously or following an injury The most common inherited factor deficiencies are the hemophilias, X-linked diseases caused by deficiency of Factor (F) VIII (hemophilia A) or Factor IX (FIX, hemophilia B) Rare congenital bleeding disorders due to deficiencies of other factors, including FII (prothrombin), FV, FVII, FX, FXI, FXIII, and fibrinogen are usually inherited in

an autosomal recessive manner (Table 110-1) Advances in characterization of the molecular bases of clotting factor deficiencies have contributed to a better understanding of the disease phenotypes and may allow more targeted therapeutic

approaches through the development of small molecules, recombinant proteins, or cell and gene-based therapies

Table 110-1 Genetic and Laboratory Characteristics of Inherited Coagulation Disorders

y Abnormalitya

Clo

tting

Factor

Deficienc

y

In heritance

Pr evalence

in General Populati

on

a PTT T T

M inimum Hemosta tic Levels

Trea tment

P lasma Half-Life

Fib

rinogen

in 1,000,000

0 mg/dL

Cryo precipitate

2 –4 d

thrombin in

2,000,000

–30% PCCs –4 d

Fac

tor V

in 1,000,000

+ /– /–

15 –20%

6 h

Fac

tor VII

in 500,000

–20%

FFP/

PCCs

4 –6 h

Fac

tor VIII

X-linked

1

in 5,000

%

FVII

I concentrate

s

8 –12 h

Fac

tor IX

X-linked

1

in 30,000

%

FIX concentrate

s

1 8–24 h

tor X in

1,000,000

Fac

tor XI

in 1,000,000

–20%

0–70 h

Fac

tor XII

D

b

6

0 h

D

b

1

50 h

Pre

kallikrein

D

b

3

5 h

Fac

tor XIII

in 2,000,000

– /–

2–

5%

Cryo precipitate

1 1–14 d

Values within normal range (–) or prolonged (+)

b

No risk for bleeding, treatment is not indicated

Abbreviations: HK, high-molecular weight kininogen; AR, autosomal

recessive; aPTT, activated partial thromboplastin time; PT, prothrombin time; TT, thrombin time; ND, not determined; FFP, fresh frozen plasma; PCCs, prothrombin complex concentrates