(pt 2) exam #5 - heme II (cls 546)

disorders of secondary hemostasis + acquired disorders w bleeding

goal of secondary hemostasis?

stable fibrin clot

2 categories of disorders in secondary hemostasis?

disorders of fibrin formation + disorders of fibrinolysis

symptoms associated with typical disorders of secondary hemostasis?

• Delayed bleeding

• Deep muscular bleeding

• Joint bleeding

how does one "get" a disorder of fibrin formation?

• Hereditary or acquired

• Quantitative or qualitative

disorders of proteins of fibrin formation classifications

• X-linked recessive

  • FVIII & FIX

• Autosomal dominant (AD)

  • VWD ; dysfibrinogenemia

• Autosomal recessive (AR)

  • All the rest

what are the expected coag screening results with disorders of secondary hemostasis? does this differentiate between qualitative and quantitative disorders?

• Prolonged PT and/or APTT

• No

what tests would you order after a prolonged PT and/or PTT?

• Platelet count, fibrinogen (if not ordered already)

• 1:1 mix

primary assays for generalized hemostatic disorders (chart)

indications for congenital bleeding disorders

• Relatives with similar bleeding symptoms

• Onset of bleeding in infancy or childhood

• Excessive bleeding from umbilical cord or circumcision wound

• Repeated hemorrhages in childhood, adulthood

• Chronic petechiae, purpura, or ecchymoses

• Bleeding into joints, central nervous system, soft tissues, peritoneum

von willebrand disease (VWD)

• Inherited hemorrhagic disorder

• Genetically and clinically heterogeneous

• Caused by a deficiency or dysfunction of VWF

• Most common hereditary bleeding disorder

  • 125 in 1 mill have VWD w bleeding symptoms

  • Autosomal dominant in most patients

  • Autosomal recessive patients more severely affected

• First described by Erik von Willebrand in 1926

(VWD) von willebrand factor

• Synthesized in the endothelial cells & megakaryocytes

• Mediates platelet adhesion

• Complexes with and stabilizes FVIII

  • Carrier protein

• Platelet adhesion with GpIb/IX/V

  • Binds to collagen and GPIB/IX

(VWD) synthesis and structure of VWF

• Synthesized by Ecs

• Multimeric chain of identical subunits

• VWF molecules bind FVIII in 1:1 ratio

• Defects in VWF may:

  • Interfere with ligand interaction

    • FVIII ; GPIB/IX

    • GPIIb/IIIa

    • Collagen ; Heparin

  • Cause bleeding by impairing either platelet adhesion or blood clotting

types of VWD

• Types 1 & 3: quantitative deficiencies of VWF

• Type 2: four subtypes ; qualitative deficiencies

type 1 & 3 VWD

• BOTH ARE QUANTITATIVE DEFICIENCIES OF VWF

• Type 1 (70-80% of cases)

  • Most common

  • Mild w partial deficiency of VWF

  • All multimers present but reduced

• Type 3 (0.5-5 per million)

  • Absolute absence of VWF and VWF:Ag

  • Severe form of disease

type 2 VWD

• Qualitative abnormalities of VWF

• VWF activity is consistently reduced

• May have normal levels of VWF protein but protein is dysfunctional

• 15-20% of cases

• Four subtypes or variants

clinical manifestations of VWD

• Usually mild bleeding symptoms which reflect a platelet problem

  • Epistaxis ; menorrhagia

  • Hemorrhage in mucosal and cutaneous tissues

  • Bleeding following tooth extraction

  • Gingival bleeding

  • Easy bruising

• Homozygotes or double heterozygotes—more severe

  • Great phenotypic variability in symptoms and lab results

VWD vs hemophilia

• NO hematoma and hemarthroses

  • Not prominent (unlike hemophilia A)

• NO major hemorrhagic tendency

  • Absence of bleeding symptoms does not rule out this diagnosis

laboratory evaluation of VWD

• Screening tests for fibrin formation

  • Do not directly evaluate VWF

• Requires a battery of tests

  • Platelet count, PT, APTT, PFA-100

  • Specific tests

    • Quantitate VWF & FVIII activity

    • Determine various functional and structural aspects of VWF protein

    • Platelet aggregation studies

• Remember we need both VWF:A and VWF:Ag for diagnosis!!

(additional testing for VWD) VWF:Ag

• Cannot measure VWF:Ag by clot-based assays

• Immunologic testing required to quantitate

  • Use monoclonal ABYs to VWF (ELISA), LIA

  • Patients ABO type affects level of VWF

    • Type O has 25-30% less than A and B

(additional testing for VWD) VWF:Rco

• VWF ristocetin cofactor activity; aka VWF activity test

  • Functional assay ; quantitative

  • measured by the ability to cause agglutination of reagent platelets by the patient’s VWF

  • Agglutination is measured in an aggregometer

VWD laboratory diagnosis

• RIPA—Ristocetin-induced platelet agglutination

  • Uses patients platelet rich plasma

  • Measures ability of ristocetin to induce agglutination of patient platelet rich plasma

    • Detects patient's VWF binding to patient's GPIb/IX

    • Abnormal in both BSS and VWD

VWD vs FVII deficiency

• APTT

  • Will be prolonged when FVIII activity is <30%

  • Often normal in VWD

• FVIII activity

  • Measured using factor assay

    • Modified APTT

    • Uses human FVIII deficiency plasma as a substrate

    • Normal levels are 50-150%

VWD diagnosis (summary)

• PFA 100 closure time

  • Uses collagen/ADP and COL/EPI to assess aggregation

  • Abnormal in VWD with both agents

• Diagnosis of VWD

  • Decreased VWF:Ag, decreased VWF activity, decreased FVIII activity, and/or prolonged PFA closure time

  • Classic case: all four laboratory tests are abnormal

VWD lab diagnosis challenges

• FVIII level is variably reduced in VWD

  • APTT

    • Typically prolonged only when FVIII <30%

    • Often normal in VWD

• PT and TT are normal

• VWF:Ag

  • Acute phase reactant

  • Blood type quandary (type has less Ag)

final step in VWD diagnosis / confirmation

• Establish subtype using SDS agarose electrophoresis

  • Evaluate multimeric structure of VWF

  • Multimers are separated by size and visualized as bands

• DNA analysis

  • Specific gene mutation on chromosome 12

  • Gene is large and complex with high degree of polymorphism--makes DNA analysis difficult

acquired von willebrand syndrome (AVWS)

• Rare ; loss of VWF secondary to:

  • Neutralizing antibodies, protein degradation, adsorption to cell surfaces

• Occurs in previously normal individuals

  • Present w new-onset bruising and bleeding

  • Reduced VWF activity, VWF:Ag and FVIII

  • Can see increased levels of VWF propeptide (VWFpp)

• Associated with:

  • Underlying lymphoproliferative disorders (CLL/SLL, MM, MGUS etc) and autoimmune disorders

therapy for VWD

• Goal: raise levels of VWF

• Cryoprecipitate

  • Classic treatment; has molecular forms of VWF, FVIII, and fibrinogen

• DDVAP (deamino-D-arginine-vasopressin or Desmopressin)

  • Preferred ; modified ADH

  • Induces endothelial cell release of VWF from Weibel-Palade bodies

  • Temporarily increases levels of VWF and FVIII

    • No effect in type 3 VWD patients

• Concentrated "intermediate purity" FVIII products

  • Contain large amounts of intermediate size VWF molecules

  • VWF levels increase after administration

  • For nonresponders to DDVAP

hemophila (general)

• X-linked recessive disorders

  • Females are carriers and pass abnormal X chromosome to sons who are affected

• Hemophilia A—VIII deficiency

  • Antihemophilic factor

• Hemophilia B—IX deficiency

  • Christmas factor

pathophysiology of hemophilia

• Insufficient generation of thrombin by FIXa/VIIIa complex through intrinsic pathway of coagulation cascade

• Results in:

  • Inadequate fibrin formation (no thrombin burst/propagation)

  • Excessive fibrinolysis due to lack of thrombin activation of TAFI

mutations in hemophilia

• Occur throughout the genes for FVIII and IX

• Males bearing single defective allele affected with hemophilia

  • Severity determined by site of mutation

  • Inherited from carrier mother or spontaneous mutation

• Hemophilic males do not transmit genes to sons

  • All daughters are obligate carriers for hemophilia

(hemophilia) factor VIII gene mutations

• Majority result in either quantitative or qualitative defects

• Most are CRM or CRM^R (cross reacting material negative or reduced) ~95%

  • i.e. quantitative!!

  • Means there is a decrease or absent clotting activity by both functional and immunological testing

  • CRM+ = normal levels of a dysfunctional FVIII

• Inversion mutation

  • Involves intron 22

  • Occurs in 50% of patients w severe disease

(hemophilia) factor IX gene mutations

• Mutations in FIX gene or its regulatory components

  • Severity dependent on type and region of mutation

  • Mutations = mild -> mod -> severe hemophilia

• 1/3 are CRM+ (qualitative defect)

  • Have the normal quantities of a dysfunctional FIX

• 2/3 are CRM- or reduced (quantitative defect)

clinical aspects of hemophilia (levels of hemophilia)

• Clinical severity corresponds with level of factor activity

  • >30% activity--no abnormal bleeding

• Severe hemophilia

  • Factor coagulant activity < 1% of normal

  • Frequent spontaneous bleeding into joints and soft tissues

  • Prolonged bleeding with trauma or surgery

• Moderate hemophilia

  • Factor coagulant activity 1–5% of normal

  • Occasional spontaneous bleeding

• Mild hemophilia

  • Factor coagulant activity > 5% of normal

  • Rare spontaneous bleeding

severe hemophilia

• Bleed from any anatomic site after negligible or unnoticed trauma

• Most common symptoms

  • Hemarthrosis--chronic inflammation, deterioration

  • Intra-articular and intramuscular bleeds

  • Soft-tissue bleeds, bleeding associated with intramuscular injections and surgery, oral bleeding, hematuria, GI tract bleeding

• Most common hemorrhagic cause of death: intercranial hemorrhage

how do hemophilia A and B present?

present the same ; diagnosis depends on:

• Unusual bleeding symptoms early in life

• Age of first bleeding varies with severity of disease

• Family history

• Physical exam

• Laboratory evaluation

laboratory evaulation of hemophilia

• PT, TT, and platelet function—normal

• APTT prolonged

  • Mild deficiencies may not be detected (levels between 20 and 50 IU/dL or >30% activity

• confirm w specific factor assays for FVIII and FIX

• Molecular diagnosis--DNA probes

• Use mixing studies to rule out inhibitor

(hemophilia) carrier detection

• Challenging to detect

• Cannot detect with plasma tests due to variability in expression

• VIII carriers

  • VWF:Ag level to FVIII level—2:1 (more vWF than VIII)

  • Genetic testing is preferred method

  • Acute phase reactant ↑ w/exercise, stress, inflammation

  • 1/3 arise from point mutations and cannot be predicted

  • Inversion of intron 22 (most common mutation)

• IX carriers

  • Direct gene sequencing

therapy for hemophilia

• Goal is replacement of clotting factor to achieve hemostasis

• Hemophilia A

  • Heat or solvent-detergent treated cryoprecipitate preparation or FVIII

• FVIII and FIX products

  • prepared using monoclonal antibodies

• Recombinant DNA technology products are preferred

• DDAVP—mild hemophilia A

• Gene therapy—showing promising results in clinical trials

(hemophilia) inhibitors

• Alloantibodies

  • Neutralize coagulant effects of replacement therapy

  • Seen in:

    • 5-20% of hemophilia A patients

    • 1-3% of hemophilia B patients

• Most often produced by pts w large deletions

  • CRM- patients have higher risk of developing an inhibitor than CRM+ patients (quantitative deficiency vs qualitative)

what tests would be prolonged in Factor I (fibrinogen) deficiency?

• PT/INR, APTT, TT

fibrinogen deficiency (general)

• Quantitative defects--type I

  • Afibrinogenemia--23%

  • Hypofibrinogenemia--26%

• Qualitative defect--type II

  • Dysfibrinogenemia--51%

  • Hypo-dysfibrinogenemia

afibrinogenemia

• No detectible fibrinogen by any method

  • Severe bleeding disorder but milder than severe hemophiliacs

• PT, APTT, TT--abnormal

  • Correct by mixing studies

• BT and plt agg studies are normal

• Definitive diagnosis

  • Antigenic and functional assays--<1 mg/dL

  • Rule out heparin contamination, fibrinogen degradation (FDPs), inhibitor

• Associated with recurrent pregnancy loss

• Therapy = cryoprecipitate or fibrinogen concentrates

hypofibrinogenemia

• 50% of normal levels of fibrinogen

• Milder bleeding course--often asymptomatic

• Associated with recurrent pregnancy loss

• acquired by:

  • Reduced/absent or abnormal fibrinogen synthesis

  • Fibrinogen loss exceeds fibrinogen production

  • Hyperfibrinolysis

dysfibrinogenemia

• Normal fibrinogen levels but abnormal structure and function (qualitative issue)

• Autosomal dominant--most often seen in heterozygous state

  • 50% are asymptomatic

  • 25% mild bleeding

  • 25% thrombosis

• Differentiate from acquired forms

  • Such as liver disease, pancreatitis, and so on

tests for dysfibrinogenemia

• PT, APTT, and PFA—usually normal

• TT, clot-based quantitative assay, reptilase time—abnormal (activity tests abnormal)

• Antigenic fibrinogen assays normal

• >600 mutations have been identified

  • Some involve:

    • The site of cleavage to fibrin (and/or release of FP A or FP B)

    • The site of polymerization of fibrin (no polymers)

    • The binding site for XIIIa cross linkage

    • Thrombin binding sites

prothrombin deficiency (FII)

• Genetically heterogeneous

  • Hypothrombinemia--quantitative

  • Dysprothrombinemia--qualitative

• Congenital prothrombin deficiency

  • Rare--1 in 2,000,000 (rarest of them all)

  • Homozygotes

    • <10% of normal--severe bleeding

    • Complete absence--incompatible with life

• Heterozygotes for hypoprothrombinemia

  • Levels of ~50% of normal--asymptomatic

(prothombin deficiency) lab results

• Prolonged PT, APTT

• Normal TT and platelet function studies

(prothrombin deficiency) diagnosis + treatment

• diagnosis

  • Specific factor assay

  • Immunologic tests for antigen

  • Exclude vitamin K deficiency

• treatment: PCC--prothrombin complex concentrates

factor V deficiency

• Disorders genetically heterogeneous (can be quantitative/qualitative)

• Lab tests

  • PT and APTT prolonged ; TT normal

• Diagnosis--specific FV assay

• Therapy—fresh frozen plasma

  • Plt products can provide FV

factor VII deficiency

• Only PT/INR is prolonged

• Rare disorder; may be quantitative or qualitative

  • Homozygous--<10 U/dL

  • Heterozygous--40-60 U/dL

• Definitive diagnosis

  • FVII assay--functional and quantitative

• Therapy

  • Recombinant FVII (NovoSeven), prothrombin complex concentrates (PCC), FVII concentrates

  • Gene therapy

FVII deficiency symptoms

• No symptoms (54%)

• Bleeding after trauma (17%)

• Mild, spontaneous bleeds, bruising, nose bleeds, abnormal menstrual periods (22%)

• Major bleeds, joint bleeding, brain bleeds, stomach intestines, and umbilical cord (7%)

factor X deficiency

• Rare disorder—quantitative or qualitative

• Lab tests

  • PT, APTT, and russel viper venom test (directly activates X)--prolonged

  • Chromogenic assay / immunological assay

  • Platelet function test--normal

• Definitive diagnosis—specific factor assay for FX

• Therapy—fresh frozen plasma and prothrombin complex concentrate (PCC)

what are the assays that can measure factor X? (5)

• PT-based

• PTT-based

• Chromogenic Factor X

• Immunological Factor X

• dRVVT

what is hemophilia C? what tests are prolonged in it?

• Deficiency in factor XI

• APTT

factor XI deficiency (hemophilia C)

• occurs most often in Ashkenazi Jews

• Autosomal recessive--affects males and females

• Most are type I--quantitative

• Lab tests—prolonged APTT, other tests are normal

• Diagnosis--specific FXI assay

• Treatment

  • FXI concentrates--available in Europe

  • FFP ; low dose rFVIIa

what test is used to detect Factor XIII deficiency?

5M urea solubility test

forms of factor XIII deficiency

highly heterogenous ; rare ; pts lack both plasma and platelet FXIII

1. Deficient of both subunits A and B (Type 1)

2. Deficiency of A subunit only (Type 2)

3. Deficiency of B subunit only (Type 3)

hallmarks of factor XIII deficiency

• Umbilical stump bleeding and bleeding after circumcision

• Intracranial hemorrhage with little or no trauma

• Recurrent spontaneous abortion

• Bleeding at time of surgery is not excessive

• Delayed bleeding can occur

(factor XIII deficiency) lab results + diagnosis

• Laboratory results

  • Normal PT, APTT, TT, and platelet function despite history of bleeding

  • Abnormal in vitro clot formation

• Diagnosis

  • Solubility of fibrin clots in 5M urea

    • Needs <1% of XIII activity to demonstrate deficiency

  • Specific assays for FXIII available

you have a normal PT but a prolonged PTT with no history of bleeding, what factors would you suspect have a deficiency?

FXII, PK, HK

combined factor deficiencies

• Vitamin K deficiency (II, VII, IX, X)

  • Factors are produced by no gamma carboxylation (non-functional)

  • PT/PTT prolonged, TT normal

• Combined V and VIII deficiency

  • Mild to moderate bleeding

  • Aka familial multiple clotting factor deficiency Type I

  • PT/PTT prolonged

disorders of fibrinolytic protein inhibitors

• a2-antiplasmin (AP) and plasminogen activator inhibitor-1 (PAI-1)

  • Impaired regulation of fibrinolysis

  • Excess plasmin activity

• Specific assays for AP and PAI-1

• Screening test: PT/PTT, specific factors are all normal, FIB can be decreased

• Results in bleeding symptoms

what does thrombin do?

• Coagulant function (fibrin formation)

• Anticoagulant fxn

• Cytokine-like activity/inflammation

• Wound healing/cellular proliferation

disseminated intravascular coagulation (DIC)

• Patient generally bleeds at same time that disseminated clotting is occurring

• Results in the uncontrolled inappropriate formation and lysis of fibrin within the blood vessels

• Clotting protein, inhibitors, and platelets CONSUMED

  • Consumed faster than they are synthesized (consumption coagulopathy)

  • Acquired deficiency of multiple hemostatic components

  • Fibrinolysis follows fibrin formation

(DIC) incidence and etiology

• 1 in 1000 hospital patients

• Most involved introduction of TF into vascular system

• Most common trigger—severe infections (septicemia)

  • Bacterial toxins and inflammatory cytokines (IL-1, IL-6, TNF) activate EC to express TF

• Other common triggers

  • Pregnancy (thromboplastin from amniotic fluid)

  • Massive tissue or blood cell injury

  • Malignancy (increased TF in the blood stream

(DIC) pathophysiology

• Initiating event

  • Generalized or systemic (NOT localized) UNREGULATED formation of thrombin

  • Consumption of its substrates

  • Fibrinogen, FV, FVIII, FXIII

  • Depletion of prothrombin, activation and aggregation of platelets

• Thrombin

  • Activates EC release of t-PA

  • Activating plasminogen → plasmin

  • Triggering aggressive secondary fibrinolysis

why does DIC occur?

results from failure of mechanisms that limit blood clotting and thrombin generation

• AT, HCII, & TM are overwhelmed

• IL-1, TNF lead to decrease of endothelial cell expression of TM

• Decreased PC/PS inhibitory system

• Increased FPA/FPB

• Increased D-dimer

symptoms of DIC

• DIC can be acute (hemorrhagic) or chronic (thrombosis)

• Clinical symptoms

  • Bleeding from multiple sites ; clots ; bruising

  • SOB ; confusion

• Fibrin strands within small vessels result in traumatic destruction of RBCs (schistocytes)

  • Microangiopathic hemolytic anemia (MAHA)

• Fibrin deposition in an obstruction of microvasculature

  • Tissue anoxia/microinfarcts

  • Renal failure, liver failure, respiratory failure, skin necrosis, gangrene, thromboembolism

lab diagnosis of DIC

• Available tests are nonspecific

  • No single or combination of tests can establish the definitive diagnosis of DIC

• PT, APTT, and TT—prolonged

• ↓ fibrinogen & ↓ AT

• D-dimer + (not specific for DIC)

• Platelet count ↓; platelet function tests abnormal

• Schistocytes, thrombocytopenia on PB smear

• Markers of ↑ coagulation (thrombin generation)

  • Not routinely available

therapy for DIC

• Eliminate underlying cause if possible

  • Acute DIC often self-limited & will disappear when fibrin is lysed

  • Replacement therapy

    • Platelets, RBCs, cryoprecipitate, or FFP

  • LMW heparin used when:

    • Predominant thromboembolic manifestation

    • Replacement therapy fails to alleviate excessive bleeding

• Mortality is still high at 50-60%--shock is common

primary fibrinogenolysis

• Must be differentiated from DIC

  • Plasminogen inappropriately activated to plasmin without concomitant thrombin generation

  • Plasmin lysis of fibrinogen, not fibrin

• Circulating plasmin will degrade

  • Fibrinogen V, VIII, XIII, other coag factors and plasma proteins

  • Relatively rare; often seen w prostate disorders, liver dx

    • Platelet count and D dimer usually normal (no fibrin formation)

• Therapy is EACA--epsilon aminocaproic acid (amicar)

  • Specific inhibitor of plasmin (dangerous if given to pts w DIC!)

products of FIBRINOGEN cleavage

• Fragment X (trinodular)

• Fragment Y (dinodular)

• Fragment D and E (unimodular)

products of FIBRIN cleavage

• DD/E

• YD/DY

• YY/DXD (most common)

• DD (most common)

liver’s role in homeostasis

• Makes majority coagulation factors

• Makes fibrinolytic proteins

• Makes inhibitors to coagulation

• Clears activated factors

liver damage & bleeding disorders

• Affects all hemostatic functions

  • Liver synthesizes procoagulant & fibrinolytic proteins

  • Liver macrophages also remove activated factors

• Laboratory test results may resemble DIC

  • Decreased production of all proteins involved in fibrin formation

  • May cause all screening coagulation tests to be prolonged

  • Platelet count +/– decreased

    • + hypersplenism, ↓ TPO

  • FDPs ↑

    • Lack of hepatic clearance of FDPs and plasminogen activators

what does vitamin K do?

• Fat soluble vitamin

• Functions as a co-factor for carboxylase (activates certain factors)

  • 2, 7, 9, 10, PS, PC, PZ

• Essential for Ca2+ binding

structure of coagulation proteins

• Catalytic domain

  • Cleaves peptide

  • Converts inactive proenzyme to active enzyme

• Non-catalytic domains

  • Regulatory segments

    • Bind Ca2+ and promote interaction with PL, cofactors, receptors and substrates

vitamin K deficiency

• Proteins are not gamma-carboxylated 

  • Ca2+ binding sites are nonfunctional

  • Called des-y-carboxy-proteins

• Induced functional deficiencies of all vitamin K-dependent proteins

  • Similar to coumadin

• Causes of vitamin K deficiency in adults

  • Malabsorptive syndromes

  • Biliary tract obstruction

  • Prolonged broad-spectrum antibiotics--abolishes normal flora

how to differentiate liver disease from vitamin K deficiency in hemostasis results?

factor V remains in normal levels in vitamin K deficiency

vitamin K deficiency in newborns

• Vitamin K deficiency bleeding (VKDB)

• Newborn hepatic immaturity

  • Associated with vitamin K-dependent factors at levels of 30–50% of normal adult levels

• Bleeding from skin, mucosal surfaces, circumcision site, ecchymoses, large intramuscular hemorrhages

• Suspected when PT or APTT more prolonged than expected for age group

(vit K deficiency) bleeding diagnosis + prevention

• Specific factor assays for II, VII, IX, and X--all markedly decreased

• Platelet count and platelet function tests--normal

• Vitamin K administered to all newborns in US standard practice

types of acquired pathologic inhibitors

• Usually IgG or rarely IgM immunoglobulins

• Inhibitors of single factors

  • Patients with inherited factor deficiencies

    • After treatment with replacement concentrates

  • Associated w diseases, drugs, pregnancy

  • Interfere with or neutralize clotting factor activity

  • Prolonged screening test not corrected by 1:1 mixture with normal plasma

    • Or correct initially but not after incubation 37C for 1-2 hours

• Anti-phospholipid antibodies/lupus or CIRC anticoagulant

who are the most common factor inhibitors?

VIII and IX

(most common inhibitors) inhibitors to factors VIII + IX

• FVIII low responders

  • Low titer antibodies that do not rise after further exposure to FVIII—give large doses to overwhelm antibody

• FVIII high responders

  • Inhibitors markedly rise foll owing further exposure

    • give FIX complex products to bypass need for FVIII

    • aka FEIBA (factor eight inhibitor bypassing activity)

therapy for factor inhibitors

• Prothrombin complex concentrates (PCC) or Recombinant FVIIa

• Bypass agent that activates FX

• Equally effective for FVI II and FI X inhibitors

(factor inhibitors) lupus anticoagulant

• Develop in 6-16% of patients w SLE

• Also seen in other autoimmune diseases, neoplasias, certain infections, certain drugs, and apparently normal individuals

• Interact with phospholipid surfaces of reagents used in APTT and sometimes PT

  • "Antiphospholipid antibodies" (APLs)

  • Usually discovered when APTT is unexpectedly prolonged

• Laboratory phenomenon

  • Not associated w clinical bleeding, rather more often associated w thrombosis