COAGULATION FACTOR DISORDERS Laboratory Evaluation:

 The factors are rarely deficient or A PT, APTT & TT: Increased
defective to the extent that B Substitution studies: Corrected with normal
coagulation is slowed plasma and adsorbed plasma but not aged
 Deficiency of Factors I, II, V, VII, VIII, IX, serum
X, XII, XIII C Fibrinogen assay: Decreased
 It can be Congenital Disorders d. Bleeding time: Variable
(Inherited) or acquired Treatment: Fresh frozen plasma,
CONGENITAL DISORDERS (HEREDITARY) cryoprecipitate, or fibrinogen concentrate
Usually impaired or abnormal production of
one factor (single factor deficiency) FACTOR II DEFICIENCY
Over 90% of all coagulation factor bleeding Clinical Manifestation: Mild hemorrhaging,
disorders caused by defect in Stage 1. The 2 ecchymoses, and mucosal bleeding
most common are Hemophilia A and von Laboratory Evaluation:
Willebrand's disease. a. PT & APTT: Increased
1. Autosomal recessive inheritance: The b. Substitution studies: Corrected with
number of affected males and females normal plasma but not adsorbed plasma or
in a family will be about equal. aged serum
2. Sex-linked recessive inheritance: More C. Thrombin Time: Normal
males than females in a family are d. Factor II Assay. Decreased
affected. Treatment. Fresh frozen plasma or
3. Autosomal dominant inheritance: An prothrombin complex concentrates
equal number of males and females in
a family are affected. FACTOR V DEFICIENCY
Clinical Manifestation. Mild to moderate
Coagulation factors disorder: bleeding with bruising and epistaxis
Congenital disorders Acquired coagulation Laboratory Evaluation
(Hereditary) disorders A PT,APTT and Stypven assay: increased
B Substitution studies. Corrected with normal
Usually impaired or Usually result from plasma, adsorbed plasma but not with aged
abnormal production underlying disease. serum
of one factor (single “acquired” C. Thrombin time: Normal
factor deficiency)
D Factor V assay: Decreased
Over 90% of all Two or more factors PT, APTT & Stypven Assay Increased
coagulation factor generally affected
bleeding disorders (multiple factor Treatment: Fresh frozen plasma
caused by defect in deficiency)
stage 1. FACTOR VII DEFICIENCY
The most 2 common Most common Clinical Manifestation: Mild to moderate
are hemophilia and factors produce in bleeding
von willebrand liver or vitamin K Laboratory Evaluation:
disease. dependent. a. PT: Increased
b. APTT Stypven Time: Normal
AUTOSOMAL RECESSIVE INHERITANCE: c. Substitution studies: Corrected with
FACTOR I DEFICIENCY normal, plasma and aged serum but
not adsorbed plasma
Clinical Manifestation: Severe hemorrhaging. d. Factor VII assay: Decreased
Hemarthrosis, ecchymoses, epistaxis, and Treatment: Fresh frozen plasma or
hematomas. Frequently diagnosed at birth prothrombin complex concentrates
due to umbilical stump hemorrhaging
FACTOR X DEFICIENCY a. PT, APTT & TT: Normal
Clinical Manifestation: Mild to severe b. Substitution studies: Corrected with
bleeding Normal plasma in absorbed Plasma
Laboratory Evaluation: but not aged serum.
a. PT, APTT & Stypven Time: Increased c. Urea solubility test (5M urea solution):
b. Substitution studies: Corrected with Abnormal
normal plasma and aged serum but d. Factor XIII assay: Decreased
not adsorbed plasma Treatment: fresh frozen plasma
c. Thrombin time: Normal
d. Factor X assay: Decreased PREKALLIKREIN DEFICIENCY
Treatment: Fresh frozen plasma or Clinical Manifestation: Asymptomatic or
prothrombin complex concentrates thromb
Laboratory Evaluation:
FACTOR XI DEFICIENCY a. PT: Normal
Rosenthal’s disease or Hemophilia C b. APTT: Increased (w/ extended incuba
< 5% of all hemophiliacs time= corrected)
Highest incidence in Jewish persons of c. Substitution studies: Corrected with
Russian decent normal
Clinical Manifestation: Mild mucosal bleeding Plasma, aged serum, and adsorbed plasma
after trauma d. Prekallikrein assay: Decreased
Laboratory Evaluation: Treatment: No therapy
a. PT: Normal
b. APTT: Increased HIGH MOLECULAR WEIGHT KININOGEN
c. Substitution studies: Corrected with DEFICIENCY
normal plasma, aged serum, and Clinical Manifestation: Asymptomatic
adsorbed plasma Laboratory Evaluation
d. Factor XI assay: Decreased A. PT Normal
Treatment: B. APTT Increased (w/ extended
a. Fresh frozen plasma incubation time increased)
b. Requires therapy only following C. Substitution studies: Corrected
childbirth or surgery. with normal plasma, aged
serum, and adsorbed plasma
FACTOR XII DEFICIENCY D. HMWK assay: Decreased
Clinical Manifestation Asymptomatic, Treatment: No therapy
thrombosis, or pulmonary emboli
Laboratory Evaluation AUTOSOMAL DOMINANT INHERITANCE
PT: Normal
APTT: Increased VON WILLEBRAND’S DISEASE
C. Substitution studies: Corrected with Occurs almost frequently as Hemophilia A.
normal plasma, aged serum and adsorbed The mutation is a defect in the VIII:R
plasma component of factor VIII.
Factor XII assay: Decreased The vairiation of vWf size results in several
Treatment: No therapy is usually required clinical sub- classification of the d/o:
A. Type I vWD
FACTOR XIII DEFICIENCY B. Type IIa and IIb vWD
Clinical Manifestation: Umbilical cord C. Type III vWD
bleeding, delayed healing, and keloid D. Platelet type variant
formation
Laboratory Evaluation:
Clinical Manifestation: Mild to severe 1. Cryoprecipitate, fresh frozen plasma,
hemorrhaging factor VIII concentrate or, 1-desamino-8-D-
Laboratory Evaluation: arginine vasopressin (DDAVP)
a. PT: Normal 2. Cryoprecipitate is a plasma-fraction
b. APTT: Normal to increased (prolonged preparation prepared by thawing FFP at 4C.
APTT test only if VIII:C activity is It contains a concentrated portion of
<20%) fibrinogen and VIII complex.
c. Bleeding time: Increased 3. Preparations rich in factor VIII:C are more
d. Aspirin tolerance test: Markedly costly but are effective
increased
e. Platelet count: Normal FACTOR IX DEFICIENCY
f. Platelet aggregation studies: Abnormal  Hemophilia B, Christmas Disease §
with ristocetin 10% of all hemophiliacs
g. Factor VIII: C: Normal to decreased  No Factor IX function
h. vWf: Ag: Decreased  Clinically indistinguishable from
Treatment: Cryoprecipitate or DDAVP hemophilia A – must do special
coagulation tests to distinguish (aged
SEX-LINKED RECESSIVE INHERITANCE plasma or adsorbed plasma studies)
 Can be acquired in coumadin therapy
FACTOR VIII DEFICIENCY and liver disease
Hemophilia A - classical Hemophilia Clinical Manifestation: Similar to factor VIII
Sex-linked recessive (carried by female, deficiency
manifested in the male) causing a marked Laboratory Evaluation.
decrease in VIII:C (anti-hemophilic factor). A. PT, Bleeding time, Platelet count,
VIII:vWf is normal Platelet aggregation studies Normal
Accounts for 85% of all hemophiliacs B. APTT Increased
There are three patterns of severity: C. Substitution studies Corrected with
Π Mild hemophilia A (w/ 6 to 30% of the normal plasma and aged serum but
normal level) not adsorbed plasma
Severe Hemophilia A (Factor VIII: C level <1% D. Factor IX assay: Decreased
of the normal level) Treatment
Moderate hemophilia A (< 5% Factor VIII A Fresh frozen plasma or prothrombin
activity) complex concentrates
Clinical Manifestation: Mild bleeding and B A correct laboratory diagnosis must be
easy bruising to severe hemorrhage, made because treatment of hemophilia B is
intracranial bleeding, and crippling different from Hemophilia A
hemarthrosis (joints)  Cryoprecipitate is deficient in Factor
Laboratory Evaluation: IX, but rich in Factor VIII complex
a. PT, Bleeding time, Platelet count, Platelet  FFP replacement therapy is the
aggregation studies, vWf: Ag assay: Normal treatment of choice because it
b. APTT: Increased contains Factor IX
C. Substitution studies: Corrected with REMEMBER!!!!!!!
normal plasma and adsorbed plasma but not
aged serum  Congenital disorders of Factors I, II, V,
d. Factor VIII: C & VIII:Ag assay: Decreased VII, X, XIII are very rarely seen and
severity of bleeding dependent upon
Note: Glass bead retention test and APTT will concentration of factor present.
differentiate vWd and hemophilia A.
Treatment:
  Congenital disorders of Factors XII, PK c. At birth ( Hemorrhagic Disease of the
and HMWK exist but Patients DO NOT Newborn)
have bleeding MALABSORPTION OF FATS
Tendencies Defective activation of the Cause: Vitamin K is a fat- soluble vitamin;
fibrinolytic system are seen (therefore an thus, if fats are not available due to biliary
increased chance of thrombosis). obstruction, prolonged diarrhea, or intestinal
disease, functional factors in the prothrombin
APTT results are often markedly prolonged in family cannot be synthesized.
the ASYMPTOMATIC patients
Clinical manifestations: Bleeding
ACQUIRED COAGULATION DISORDERS Laboratory evaluation.
Usually result from underlying disease 1. PT: Increased
-"acquired" 2. APTT: Increased
Two or more factors generally affected Treatment: Vitamin K administration.
(multiple factor deficiency)
Most common factors produced in liver or STERILE GUT SYNDROME
Vitamin K dependent Cause: Antibodies may eliminate normal
intestine flora that produce vitamin K; thus,
LIVER DISEASE: functional factors in the prothrombin family
Cause: Since most coagulation factors are cannot be synthesized.
synthesized in the liver, liver disease causes Clinical manifestations: Oozing from
decreased synthesis of these factors (I, II, V, venipuncture sites and mucosal bleeding
VII, IX, X, XI, XII, XIII, PK, HMWK) and also AT Laboratory evaluation.
III, the antiplasmins, plasminogen. There is a. PT: Increased
enhanced destruction (primary fibrinolysis) b. APTT: Increased
of these factors. Treatment: Vitamin k administration
Clinical manifestations: Hemorrhage, purpura
and petechiae HEMORRHAGIC DISEASE OF THE NEWBORN
Note: severe liver disease often causes Cause: The infant has an immature liver,
decreased fibrinogen production limited vitamin K storage, and inadequate
(hypofibrinogenemia) or an abnormal vitamin K- producing intestinal flora; thus,
fibrinogen molecule (dysfibrinogemia). functional factors in
Laboratory evaluation: The prothrombin family cannot be
1. Liver enzymes synthesized.
2. Bilirubin: Increased Clinical manifestations: Umbilical stump
3. PT: prolonged (a decrease in factor VII bleeding, cephalhematoma, and bleeding
occurs because it has the shortest half-life) after circumcision.
4. APTT: Variable (in severe liver disease and Laboratory evaluation
in lat stages, the APTT is prolonged) a. PT: Increased
5. Peripheral blood smear: Codocytes (target b. APTT: Normal to increased
cells) c. Bleeding time: Normal
Treatment: Supportive. d. Platelet count: Normal
Treatment: Vitamin K administration.
VITAMIN K DEFICIENCY:
II, VII, IX and X (also Protein C &S) deficiency ACQUIRED CIRCULATING INHIBITORS
Sources are: Circulating anticoagulants which may
a. Diet (Malabsorption of fats) develop against any clotting factor
b. Intestinal bacterial flora (sterile gut Classified as autoantibodies (IgG) not
syndrome) normally synthesized by the body, bind with
the factors making them unavailable for use 6. Peripheral blood smear: Fragmented RBCs
in the cascade Note: No specific test for DIC, but FDP is the
Occur in hemophilia, SLE, drug reaction, most helpful
asthma, RA, but also in normal patients Treatment: Elimination or control of the
primary disorder
LUPUS INHIBITOR
Seen in patients with autoimmune diseases, COAGULATION INITIATED BY
drug reactions but also in normal patients Endothelial injury (intrinsic), Tissue injury
Antibodies DO NOT bind coagulation factors (extrinsic) RBC, WBC, PLT injury §Presence of
but interfere with phospholipid-dependent foreign particle or substance in the
reagents used in coagulation lab tests. circulation
Patients have NO in vivo bleeding problems
(though some have an increase risk of Causes:
thrombosis) 1. Obstetric usually due to major tissue
In vitro, any coagulation test using damage such as retained dead fetus,
phospholipid reagent will be falsely abruptio placentae or placenta previa
prolonged (PT, APTT) 2. Acute leukemias Promyelocytic - increase
Coagulation studies must be performed using number of granules released into circulation
reagents that DO NOT contain phospholipids as cells break down
3. Intravascular hemolysis (ex. transfusion
DISSEMINATED INTRAVASCULAR reaction)
COAGULATION 4. Septicemias and infection viral, bacterial,
(DIC) ricketssial, fungal, protozoan (esp. gram
Pathological Syndrome: negative that release endotoxins)
a. Uncontrolled and life-threatening 5. Massive trauma (especially crushing
formation of fibrin clots or thrombus in injuries), burns, surgical procedures
circulating blood- small and large vessels 6. Tumors-foreign tissues and cells
thrombosis with impairment of blood flow 7. Heat stroke
and possible organ damage 8.Prosthetic devices (heart valve, aortic
b. Consumption of factors and platelets balloon, peritoneal shunting)
resulting in hemorrhage 9. Vascular disease- Damaged endothelial
c. Activation of fibrinolytic system to break lining.
down the excessive clots. Large amounts of
FDP formed due to large number of clots
being broken down
Due to presence of thrombin in the
circulation. Thromboplastic material enters
circulation and initiates coagulation
DIC is classified as a consumption
coagulopathy because it results in a
depletion of platelets as well as plasma
coagulation factors.
Clinical manifestation: Purpura and bleeding
Laboratory evaluation:
1. PT & APTT: Increased
2. TT: Increased
3. Fibrinogen assay & Platelet Ct.: Decreased
4. Fibrin (ogen) split products: Positive
5. D- Dimer: Positive