HRS 02: Acquired Coagulation Disorders

Case 1:
48 woman, oral bleeding after extraction of 2 molars, spontaneous bleeding 3 weeks before
tooth extraction, anemia s/p2uRBC. 3x er for bleeding
3rd er  intubated
PMH: HIV
s/p chole, NSD, prior tooth extraction without bleeding
Meds: efavirenz, emtricitabine, tenofovir
FHx no bleeding disoders

Intubated, swollen face/eyes, massive cheeks, neck & arms

Blood from month, lips swollen, blood from nose
Ecchymoses all over

CT Scan: bilateral subdural hematoma

CBC 6/7400/350k
PT 15 seconds INR 1.2
PTT 90 seconds

PT and PTT meet at X (Factor 10) with V (Factor 5)  which II (prothrombin) to thrombin 
which cleaves I (fibrinogen) to fibrin (insoluble  clashing out to form clot)

PTT – is a tenet
- Twelve, eleven, nine, eight

PTT mixing  PTT 39 sec (25-35)

 Factor Deficiency is a trap

 not really fully corrected
 inhibitor may be present

1:1 immediate: 39
2hrs incubation: 52 seconds
 Reincubation is not always seen, but characteristic of acquired hemophilia

Factor VIII <1%

Factor IX 101% inhibitory pattern
Factor 89%

Acquired Hemophilia – isolated PTT, normal PT, fail to correct in mixing (reprolongs at 37C),
factor 8 low, Bethesda assay
Incidence is 1 in a million
60-67 of age
Bleeding
- Hemarthroses are rare
- Mucocutaneous bleeding is common
o GI Bleed, epistaxis, ecchymosis, hematuria
- Severe intramuscular bleeding  compartment
- Intracranial hemorrhage
- Postsurgical/postpartum
High mortality due to comorbid condition
50% of cases
- Autoimmune disorders
- Malignant condition
- Drug
- Infection
- Postpartum
- Post surgical
50% are idiopathic

If you biopsy  cant hemostasis

Indicative of non specific inhibitor

Betheseda assay – is logarithmic

Factor 8 Acquired Inhibitor
- Suspect in older patients without history of bleeding
- Make the diagnosis
- Increase f8 levels
o Desmopressin (5-10 years ago)
o Factor concentrate if low (5-10 years)
o Recombinant porcine B domain delected (obizur)
 Oct 2014
 Rapid factor 8 assays
 Replacement therapy not bypassing
 PK-dosing

- Use bypassing agents in attempt to achieve hemostasis
- Eradicate inhibitor
o Immunosuppression
o May remit spontaneously
o Early inhibitor eradication
 Unless childbirth or drug
 EACH2 registry: prednisone+ cyclophosphamide more CR than prednisone
alone
Factor 8 52.6
Factor 9 277%

Patient doesn’t have inhibitor to factor9

PT 18.9 (11-14)
aPTT 73.4 (22.6-32.4)
immediate 51
incubated 53

factor 2 84% NORMAL

FACTOR 5 162
FACTOR 7 69%
F8 <1%
F9 52%
F10 75%
F11 52
F12 48
INHIBITORY PATTERN NOTED IN 5,9,11,12 -non specific inhibitors

DRVVT 66.2 (0-35)

DRVVT confirm (with phospholipid) 37
Ratio 1.79 ( 0-1.14) positiive

Lupus apt 105.9

w/o PL 110
w/ PL 75
difference 35 (-13.3-7.9) positive
aPL antibodies – directed on plasma proteins are uncovered by binding of proteins to anionic
phospholipids on plasma membranes
clinically relevant antibodies
- Lupus anticoagulant = lupus inhibitor = phospholipid dependent inhibitor
o Prolong clotting in phospholipid depdent assasy, shortened by addition of
exogenous phospholipid
o Since each assay can miss 30% of cases we must o 2 assays, so you do LA-PTT and
DRVVT
- Anticardiolipin IgG or IgM
- Anti-b2gp IgG IgM

LA-PTT
- Ptt assay with reagent kit sensitivie to antiphospholipid antibody, if prolonged do
confirmatory assay with PL
- We subtract, value should be <7.9

DRVVT
- Dilute russel’s viper venom will activate f10 to f10a which will then go to activate
prothrombin to thrombin  cleave fibrinogen to fibrin
- If prolonged, do with and without PL
- Divide value with PL with w/o PL, get ratio, <1.15

apL rules
- Only one assay positive, more assays positive, worst thrombotic risk
- Triple positive are the worst
- If positive, repeat assay 12 weeks BEFORE you give diagnosis of APLA syndrome
- For lupus anticoagulant, only one assay has to be positive – there should be
phospholipid dependence
-

Interpretation: phospholipid inhibitor = lupus anticoagulant

PFA-100 (primary hemostasis in a test tube)

Collagen/epinephrine >230 (84-178)
Collagen/ADP >228 (60-107)
Infinitely prolonged

- cessation of blood flow in a microcapillary membrane

- Measure to test primary hemostasis
- Designed to replace bleeding time
- Prolonged via platlet dysfunction or vWD
- If hct <30 or if platelet <100  abnormal
- Assay must be run within 4 hrs of sample draw
 - WHOLE blood not plasma

Vwf antigen 18 (50-199)

Vwf activity <9 (50-199)

Low

Summary lupus anticoagulant + vwd deficiency = potential plasma cell dyscrasia

Monoclonal igg lamba
MGUS
Lupus inhibitor
Acquired vwd secondary to MGUS
- Typically with IVIG

Acquired VWD
- MGUS/ Myeloma
- Hypothyroidism
o Type 1 vwd – lack of protein synthesis
- Myeloproliferative disorders – sticky platelet bind high MW VWF  clearance of VWF 
type 2 (1M+)
- Valvular disorder – shearing high MW VWF  type 2 or GI AVM
- Left ventricular assist devices
o 1 in 2 patients
- Wilm’s Tumors

Amyloidosis can lead to acquired Factor 10 deficiency

- Amyloid act as a sponge and pulls out all of factor 10
- Binding and removes 10 in circulation
- Deficiency not inhibitor, Fx is removed not inhibited
- There will be correction 1:1
Treatment
- X10 replacement with PCC (off label)
o 3 factor PCC or 4 factor PCC (virally inactivated plasma derived products
- Coagadex – F10 concentrate
- F10 half-life is different for each patients due to amyloid concentration
o May be much lower than 40-45 hours in normal individuals
 o PK studies should be done for optimal dosing

Lupus inhibitor with something else

- If it’s purely lupus inhibitor  there will no correction of PT
Can be 2,5,7 deficiency

But the only one associated with lupus inhibitor is

Acquired prothrombin deficiency! (Factor 2 deficiency)

- Associated with lupus inhibitor
- Patients with a lupus inhibitor has no increased risk abnormal bleeding but there is a
rare lupus inhibitor who also have prothrombin antibody
- This F2 doesn’t block, but increase accelerated clearance
- Thus PT will be prolonged and will be corrected with risk
Lupus inhibitor + Acquired Hemophilia A