Secondary Hemostasis Disorders Inh,

 Secondary Hemostasis Disorders a

Facto
1. Coagulation factor deficiencies m
r
2. Von Willebrand’s disease pl
defici
3. Factor V Leiden e
ency
4. Circulating Inhibitors
Part 1 – Hemorrhage
5. Thrombotic disorders
Chapter 38
Primary H.D. vs. Secondary H.D.
Hemorrhage
SECO  Severe bleeding
NDAR  Classified as:
Y  Localized – from a single location
PRIMARY
HEM (injury, tumor)
C HEMOST
OSTA  Generalized – from multiple sites
H ASIS
SIS ▪ Mucocutaneous – petechiae,
A (PLATELE
(COA purpura, ecchymosis
R T/VASCU
GULA
LAR)
TION ▪ Anatomic (soft tissues) –
FACT delayed or recurrent bleeding
OR) caused by coagulopathies
Spontane  Congenital – inherited (diagnosed
O
ous, Delay during infancy)
ns
Immediat ed
et
e  Acquired – secondary to other
Skin and conditions
Deep (occurs after childhood)
Sit Mucous
Tissue
es Membra NOTES
s
ne LOCATION
Petechia Loc – infection, trauma, isolated BV defect.
Fo e, Muco – often seen in primary hemostasis disorder
Hema SOURCE
r Purpura/
tomas Ana – in coag factor deficiency.
m Ecchymo
sis Mild congenital dso – asymptomatic but effects occurs
during late stage of life after trauma, injuries or
M surgeries.
uc
Common
o Less
(nasal,or
us comm
al,GIT,GU
M on
T)
e
m
Ot
Joint,
he
muscl
r Rare
e,
sit
CNS
es
Cli Thrombo Liver  Acquired Coagulopathies
ni cytopeni Disea
ca a, vWD, se,  Secondary to infection, trauma, injuries, drug
l Scurvy Circul exposure or chronic diseases.
Ex ating  ACOTS– Acute Coagulopathy Of Trauma-Shock
  Triggered by combination of injury-
related acute inflammation, platelet
activation, TF release, hypothermia,
acidosis, and hypoperfusion.
 Treated with blood transfusion (pRBC,
FFP, PC)
 Secondary to infection, trauma, injuries, drug
exposure or chronic diseases.
 ACOTS– Acute Coagulopathy Of Trauma-Shock
 Triggered by combination of injury-
related acute inflammation, platelet
activation, TF release, hypothermia,
acidosis, and hypoperfusion.
 Treated with blood transfusion (pRBC,
FFP, PC)
 Liver Disease – hepatitis, cirrhosis, obstructive
jaundice, cancer, poisoning, congenital dso of
bili metab. etc,.
 Production of des-y-carboxyl (abn.
Form of vitamin-k dependent
coag.factors and regulators)
 Factor VII – most affected in liver dse.
 Factor V – more specific marker of liver
disease
 Dysfibrinogenemia – abnormal
fibrinogen coated with excessive sialic
acid w/c functions poorly.
 Hypofibrinogenemia (<100mg/dL) –
marker of liver failure
 Most prevalent congenital
bleeding disorder
 Qualitative or Quantitative
 Characterized by mucocu-
taneous bleeding: epistaxis
ecchymosis, menorrhagia,
GIT bleeding, hematemesis,
and surgical bleeding.
  Qualitative vWF abnormalities

 Rare Mutations in A1 structural domain

of vWF mol. Which ENHANCES THE
AFFINITY to
GP Ib/IX/V complex of platelet.

 Chronic platelet activation 

mod.thrombocytopenia

 Same mechanisms as pseudo-vWD or

platelet-type vWD – Increased
GPIb/IX/V affinity to normal vWF
multimers.

V. Subtype 2M vWD

 Qualitative vWF abnormalities

Von Willebrand’s Disease
 Decreased platelet receptor binding
I. Type 1 vWD
VI. Subtype 2N vWD
 Quantitative vWF deficiency caused by
one of autosomal dominant nonsense  Normandy Variant
mutations or deletions.  Autosomal Hemophilia
 Seen in 75% of vWD patients.  Rare autosomal vWF missense mutation
 Mild to moderate bleeding with IMPAIRED Factor VIII binding site.

 Menorrhagia is common in women with Autosomal hemophilia – because clinical

type 1 symptoms are same from hemophilia EXCEPT
It AFFECTS BOTH MEN AND WOMEN
II. Type 2 vWD
WOMEN – if diagnosed with hemophilia after
 Qualitative vWF abnormalities soft tissue bleeding symptoms
 Level may be normal to slightly MEN – misdiagnosed hemophilia and fails to
decreased respond to FACTOR VIII concentrate
 Function is consistently reduced VII. Type 3 vWD
 VWF Activity = Decreased  Autosomal recessive vWF gene
III. Subtype 2A vWD translation or deletion

 Qualitative vWF abnormalities  Severe mucocutaneous and anatomic

hemorrhage
 Mutations in A2 structural domain of
vWF mol  vWF is ABSENT or nearly absent IN
PLASMA
 10-20% of vWD
 Both primary & secondary hemostasis
 More susceptible to ADAMTS-13  are impaired.
more small-molecular weight multimers
in plasma Laboratory Assay for vWD

IV. Subtype 2B vWD  CBC, PT and PTT for screening

 Standard vWD test panel:

  Quantitative vWF test (VWF:Ag Assay)  Treatment  Plasma and Platelet
Concetrate
 VWF Activity test (VWF:RCo Assay)
Factor VII Deficiency
 Factor VIII activity assay
 Less than 30% conc/activity

 Causes moderate to severe anatomic

bleeding

 Prolonged – PT ; Normal - PTT

 Treatment  NovoSeven, Plasma,

Prothrombin complex concentrate

Factor VIII Deficiency

 Hemophilia A / Classic Hemophilia

(85%)

 Levels of Less than 1% F.VIII = Severe

(neonate)
Coagulation Factor Deficiencies
 Levels of 1% - 5% F.VIII = Moderate
Factor I Deficiency (childhood)
 Hypofibrinogenemia (<100 mg/dL) –  Levels of 5% - 30% F.VIII = Mild
dec.production hemophilia (Bleeding after surgeries or
trauma)
 Afibrinogenemia – no measurable
fibrinogen  SYMPTOMATIC HEMOPHILIA – common
in MALE only
 Dysfibrinogenemia – (<100 mg/dL) –
abn. forms  Lab Results:
PT and TT = Normal
 Prolonged PT, PTT, TT and Reptilase
PTT=Prolonged
Time
Coagulation Factor Deficiency (Hemophilia A)
 Therapy  Cryoprecipitate and/or
Fibrinogen conc. Hemophilia A - MALES
Factor II Deficiency  Male hemizygotes – experience
anatomic bleeding
 Prothrombin deficiency
 Father with Hemophilia A (non carrier
 Less than 30% conc/activity
wife):
 Prolonged PT and PTT
▪ ALL SONS ARE NORMAL
 Treatment  Prothrombin complex
▪ ALL DAUGHTERS ARE CARRIERS
concentrate or Plasma
 Father w/ Hemophilia A + Carrier Wife:
Factor V Deficiency
▪ Hemophilic Children – rare
 Less than 30% conc/activity
cases
 Prolonged – PT and PTT
Hemophilia A – FEMALES (carriers)
 If caused by thrombocytopenia – PLT
 Female heterzygotes – no bleeding
Decreased, PT and PTT are prolonged
  Carrier Mother with unaffected  Lab results:
Husband: PT = Normal
PTT = Prolonged
▪ 25% Normal Daughter
Factor XII Deficiency
▪ 25% Normal Son
 Less than 1% of conc/activity
 Mostly detected by factor VIII:vWF ratio
 Causes moderate to severe anatomic
Clinical manifestations
bleeding
 Hemarthroses
 Markedly Prolonged – PTT
 Hematomas
 Treatment  Plasma or Cryo every 3
 CNS bleeding weeks

 GIT, peritonium and renal Bleeding Factor XIII Deficiency

Factor IX Deficiency  Lab Results:

PT, PTT and TT = Normal
 Hemophilia B / CHRISTMAS DISEASE 5M Urea Solubility = Soluble
(14%) (2hrs dissolved)
 A sex-linked disorder

 Mild to severe bleeding

 Lab results:
PT = Normal
PTT = Prolonged

Factor X Deficiency

 Less than 30% conc/activity

 Causes severe anatomic bleeding

 Described in amyloidosis,
paraproteinemia, and antifungal drug
therapy

 Prolonged – PT and PTT & Russel Viper

Venom Time

 Treatment  Plasma or Prothrombin

complex concentrate to raise to 75%

Factor XI Deficiency

 Hemophilia C / ROSENTHAL DISEASE

(1%)

 Autosomal dominant

 Mild to moderate bleeding

Laboratory Results of Coagulation Factor Deficiency

 Circulating Inhibitors

Factor VIII inhibitor:

 Mostly IgG4, non-complement fixing,

warm-reacting Abs.

 Mixing studies = Prolonged PTT not

corrected by normal or adsorbed
plasma and aged serum.

 Bethesda Assay – used to quantitate the

inhibitor

Lupus Anticoagulant

 Antiphospholipid antibodies – binds

protein-PPL complexes. (nonspecific
inhibitors)

 Characterized by ischemic attacks,

strokes, coronary and peripheral artery
disease, venous thromboembolism,
spontaneous abortions.

 IgM, IgG or IgA types

Part 2 – Thrombosis
Chapter 39

Thrombosis

 Inappropriate formation of platelet or fibrin

clots that obstruct blood vessels.

 These could cause Ischemia and Necrosis.

 Thrombophilia (Hypercoagulability)

 Predisposition to thrombosis secondary

to acquired or congenital disorders.

Theoretical Thrombophilia causes:

 Deep vein thrombosis (DVT)

 Most prevalent venous

thromboembolic events

 Caused by clots formed in iliac,

popliteal, and femoral veins of calf

 Emboli – Fragments of thrombi

 Arterial Thrombotic Disease

 Peripheral vascular occlusion, MI,

Cerebrovascular Ischemia.

Thrombophilia

 Factor V Leiden

 Aka hereditary resistance to APC or

APC Resistance Leiden Type.

 Most common inherited thrombophilia

 An abnormal mutation in R506Q gene

necessary for developing coag factor V.

 Arginine in position 506 – Normal

 Glutamine in pos.506 – Factor V Leiden

 Resulting to resistance to APC 

uncontrolled clot formation 
Thrombosis.