Hemorrhagic

Coagulation
Disorders

Hemorrhage
oSevere form of bleeding that requires intervention
oA loss of large amount of blood from the vessels, either
externally or internally

Classification of
Hemorrhage
oLOCALIZED VS GENERALIZED
oMUCOCUTANEOUS VS ANATOMIC
oACQUIRED VS CONGENITAL

LOCALIZED
oHemorrhage from a single location
oIndicates injury, infection, tumor or an isolated blood
vessel defect
oEx: surgical sites that bleeds excessively due to
ineffective suture

GENERALIZED
oBleeding from multiple sites
oSpontaneous and recurring bleeds
oRequires physical intervention and transfusions
oCOAGULOPATHIES disorders of primary or secondary
hemostasis that exhibits generalized bleeding
oPrimary Mucocutaneous
oSecondary Anatomic

Generalized bleeding
signs
oPurpura or petechiae (< 3mm)
oEcchymoses (>3mm)
oEpistaxis recurrent nosebleeds; last longer than 10
mins
oRecurrent or excessive bleeding from trauma, sugery or
dental extraction
oSimultaneous hemorrhage from several sites
oMenorrhagia menstrual hemorrhage
oHematemesis vomiting of blood

MUCOCUTANEOUS (1)
oManifests as bruises or purpura (purple lesions of the
skin caused by extravasated RBCs)
oAssociated with thrombocytopenia, qualitative plt
disorders, VW dse and vascular disorder (scurvy or
telangiectasia)
Ex:
oMenorrhagia menstrual hemorrhage
oHematemesis vomiting of blood
oEpistaxis recurrent nosebleeds; last longer than 10
mins

ANATOMIC (2)
oSoft tissue hemorrhage
oSeen in acquired or congenital defects
oEx: Recurrent or excessive bleeding from trauma, sugery or
dental extraction
oSIGNS
Repeated join bleeds (hemarthroses) inflamed/swellimmobilized
Soft tissues (muscle/fat) nerve compression loss of function
Body cavities depends on the organ affected
CNS headache, confusion, seizure and coma
Kidneys hematuria (acute renal failure)

Screening tests:
oHgb, Hct, Retics ct anemia associated with chronic
bleeding; bone marrow response
oPlt ct thrombocytopenia
oPT def of F 2,5,7 and 10 (prolonged CT)
oPTT def of all factors except F 7 and 13 (prolonged CT)
oThrombin time hypo and dysfibrinogenemia

ACQUIRED
oAdult onset ; associated with another dse; not found in
relatives
oEx:
oLiver disease
oDIC
oRenal Failure
oNephrotic syndrome
oVit K def
oAcquired Hemophilia and VWD

Liver dse
oMay be localized or generalized; muco or anatomic
oEsophageal varices enlarged and collateral esophageal
vessles; complication of chronic alcoholic cirrhosis
(localized)
oHepatosplenomegaly?
oMuco- assos. with thrombocytopenia
oSoft tissue bleeding is the consequence of procoagulant
dysfunction and def

Liver dse
oLiver- produce nearly all plasma coag factors and
regulatory proteins
oAlters the production of VIT K dependent factors
(prothrombin grp F 10, 9, 7, 2) and control proteins
C,S,Z
oDES GAMMA CARBOXYL FORM
o PIVKA
o W/o 2nd carboxyl grp (due to deficient gamma-carboxylation) Impt for Ca and PL binding
o Altered structure which makes the factors ineffective for coag

Liver dse
oF 7 - shortest half life of 6 hours; first coag F to exhibit
decrease act. ; early sensitive marker in mild liver dse (PT)
o7>9>10>2 (decreasing)
oF 5 more specific marker bec it is NON-VIT K dependent
and is not affected by Vit K def
oFibrinogen APR frequently elevated in early or mild liver
dse. However in end stage, it may fall to <100 mg/dl, a
mark for LIVER FAILURE
oDysfibrinogenemia fibrogen coated with excessive sialic
acid (prolonged TT & RT)
oVWF, F 8 and 13 maybe unaffected or elevated in mild to
moderate liver dse

Liver dse
oPLT moderate thrombocytopenia (<150,000/mcL)
result from sequestration and shortened plt survival
assos. with portal hypertension and resultant
hepatosplenomegaly
oAcute alcohol toxicity also suppresses plt prodn ; plt
aggregation and secretion also suppressed
oAggregometry may be used to predict bleeding and
thrombosis risk
oD-dimer >240 ng/mL
oEuglobin clot lysis time lysis in <2 hr

Liver dse
oTx:
1. oral or IV vit K therapy
2. FP transfusion provides all coag F; a unit is consists
of 200 to 280 mL; adult = 2 units
3. Cryoprecipitate small volume and high Fibrinogen
conc.; less allergic transfusion rxn (also the component
of choice for hypofibrinogenemia); Administer when
Fibro= 50 mg/dl
4. Plt concentrates, prothrombin complex concentrates,
activated protein C and antithrombin concentrates

DIC
oAcute, uncompensated PT, PTT and TT prolonged;
Fibrinogen <100 mg/dL; fibrin degradation products inc.
D-dimers are increased)
oChronic, compensated the only elevated result may be
D-dimer assay value (hallmark of unregulated coag and
fibrinolysis)
oSignificant complication of liver dse caused by decreased
liver prodn of unregulatory antithrombin, protein C and S
and by the release of activated procoag from
degenerating liver cells; the failing liver cannot clear
activated coag factors
oTX: administer RBCs, FP, plt concentrates, activated pro
C and antithrombin concentrates

Renal Failure
oAcute renal failure assos. with GI bleeding caused by
specific anatomic lesions but this not necessarily indicate
coag or plt dysfunction
oChronic renal failure assos. with plt dysfunction and
mild to moderate mucocutanous bleeding
oPlt adhesion and aggregation are suppressed (plt are
coated with guanidosuccinic acid or dialyzable phenolic
compounds)
oAnemia and thrombocytopenia (can be corrected by
dialysis, EPO or RBC transfusion and IL-11 therapy (used
for tx of pxs with chemotherapy induced
thrombocytopenia)

Renal Failure
LAB TEST RESULT:
oBT may be prolonged (too unreliable)
oPT and PTT normal
Tx:
1. Dialysis
2. DDVAP IV or intranasal VWF plt adhesion
Contraindication: Aspirin, Clopidrogel or other plt inhibitors
increase the risk of hemorrhage

Nephrotic Sydrome
oDisruption of electrical charges that produce the tightly
fitting podocyte barrier resulting to massive loss of
proteins and lipids into urine
oState of increased glomerular permeability; Low
molecular wt CHONS are lost through the glomerulus
oF 2, 7,9,10 and 12 can be detected in the urine

Vit. K def
oUbiquitous in food; daily reqt is small
oNewborns = vit. K deficient
oVIT. K ANTAGONISTS: warfarin (disrupts the vit K epoxide
reductase) and vit K quinone reductase rxn
oIn deficient gamma-carboxylation, liver releases
dysfunctional des-gamma carboxyl F (prothrombin grp
and C,S,Z); these inactive forms are called PIVKA
(proteins in vit K antagonism)

Vit. K def
LAB TESTS RESULT:
oPT (prolonged) / with or without prolonged PTT
oF 7>9>10>2
Tx:
1. Oral or intravenous vit. K
2. FP (in case of severe bleeding)

Acquired Hemophilia
oPx (older than age 60 and no underlying dse) produces Ab to F
VIII ;
oAssos. with RA, SLE, inflammatory bowel dse and
lymphoproliferative dse
o1 per 1 million people per year
oS/sx: bleeding in GI or GU tract
Lab Test Result:
oprolonged PTT; normal PT and TT; F VIII assay (<30%)
Tx:
oDDVAP ; F 8 concentrates; Immunosupressives; Plasma exchange

Other Factor Inhibitors

oAntiprothrombin Ab not assos. with lupus anticoag are
rare
oF 2 & 5 Ab exposure to topic bovine thrombin or fibrin
glue
oAutoanti-X Ab - rare

Acquired von Willebrand

dse
oAssos. with hypothyroidism, autoimmune, lymphoproliferative
and myeloproliferative disorders
oCause: Decrease VWF, presence of autoantibodies or
adsorption of VWF to abnormal cell surfaces
oModerate to severe mucocutaneous bleeding
Lab Test Result:
oPTT (moderately prolonged); PT (not affected); diminished VWF
activity and presence of VWF antigen by IA
Tx:
oDDVAP, F 8/VWF concentrates; cryoppt (no longer
recommended)

CONGENITAL
oUncommon ; occurring in 1 per 100 people
oDiagnosed in infants or young children who often have
relatives with similar symptoms
oLead to repeated hemorrhages
oEx:
oVWD, F 8 and 9 def (hemophilia A and B) and plt function
disorders

von Willebrand dse

oCommon mucocutaneous bleeding disorder
oBoth quantitative and structural abnormalities lead to
decrease adhesion by plt to injured vessel walls causing
impaired primary hemostasis
oMost prevalent (1%); Lowest Type O and highest AB
oVWF
oglycoprotein (800,000 to 20 million D); largest molecule
o 0.5 to 1.0 mg/dL
oSynthesized in the ER of endothelial cells and stored in
weibel-palade bodies of endothelial cells & in
megakaryocyte stored in alpha granules of plt
oChromosome 12 ; F 8 carrier molecule

von Willebrand dse

oReduce plt adhesion leads to mucocutaneous
hemorrhage
oTYPES:
o1 quantitative
o2 qualitative ; 4 subtypes
o3 autosomal recessive VWF gene translation or deletion
mutations

Nomenclature
oVIII/VWF : combination of VIII and VWF
oVIII : protein transported on VWF
oVWF:Ag : antigenic basis
oVWF: Rco : Ristocetin cofactor act
oVIII:C : F VIII coagulant act

Lab Detection
oDefintive Dx: personal and family history, CBC, PT and
PTT
oStandard VWD test panel:
1. Quantitative VWF test (VMF: Ag assay)
2. VWF activity test (ability to bind to plt; VWF: Rco assay
(employs rgt plts)
3. Factor 8 activity assays
o.VWF act: influenced by ABO blood grp, inflammation,
hormones, age, and physical stress

Treatment
oMild (RICE: rest, ice, compression and elevation)
oModerate: estrogen and DDVAP
oSevere: Plasma derived preparations (Humate-P,
Alphanate and Wilate)

Hemophilia A
o85% ; second to VWD in prevalence
oCongential deficiency of Factor 8
oAka Classic Hemophilia
oMale hemizygotes experience anatomic bleeding

Hemophilia B
oFactor IX deficiency
oAlso called Christmas dse
o14%

Hemophilia C
oFactor XI deficiency
oAshkenazi Jews
oRosenthal disease