Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (67 page)

>100 mg/dL) and
platelets
; no role for activated protein C in sepsis (
NEJM
2012;366:2055)

Vitamin K deficiency

• Etiologies: malnutrition, ↓ absorption (
antibiotic
suppression of vitamin K-producing intestinal flora or malabsorption), liver disease (↓ stores),
warfarin

HYPERCOAGULABLE STATES

Suspect in Pts with venous or arterial thrombosis at young age or unusual locations
,
recurrent thromboses or pregnancy loss or
FHx

Diagnostic evaluation
(not routinely required for initial VTE)
• APC resistance screen; prothrombin PCR test; functional assays for proteins C and S, ATIII; homocysteine level; factor VIII levels; anticardiolipin and lupus anticoagulant Ab.  Also consider nephrotic syndrome, PNH (esp. if mesenteric thrombus).

• Consider
JAK2
mutation testing if suspect MPN or splanchnic thrombosis.

• Proteins C & S and ATIII levels are affected by acute thrombosis and anticoagulation ∴ levels best assessed ≥2 wk after completing anticoagulation course • Age-appropriate malignancy screening (
in 7–10% in “idiopathic” DVT;
Annals
2008;149:323)
Treatment

• Asx w/ inherited risk factor: consider prophylactic anticoag. if develops acquired risk factor • Thrombosis w/ inherited risk factor: see “Venous Thromboembolism”

Antiphospholipid syndrome (APS)
( 
J Thromb Haemost
2006;4:295;
NEJM
2013;368:1033)
• Definition: dx requires ≥1 clinical & ≥1 laboratory criteria

Clinical: thrombosis (any) or complication of pregnancy (≥3 spont. abortions before 10 wk or ≥1 fetal loss after 10 wk or premature birth before 34 wk)

Laboratory:
moderate–high titer anticardiolipin (ACL),
lupus anticoagulant (LA) or β
₂
-glycoprotein-I (β
₂
-GP-I) Ab on ≥2 occasions at least 12 wk apart

• Clinical:
DVT
/
PE
/
CVA
,
recurrent fetal loss
,
thrombocytopenia
, hemolytic anemia, livedo reticularis; “
catastrophic APS
” = ≥3 organ systems in <1 wk w/
APLA & tissue microthrombi (
Lupus
2003;12:530) → 44% mortality (
Arth Rheum 2006
;54:2568) •
Antiphospholipid antibodies (APLA)
✓
if: SLE, age
<
40 y & arterial thromb, recurrent venous thromb, spontaneous abortion

ACL: Ab against cardiolipin, a mitochondrial phospholipid; IgG more specific than IgM

LA: Ab that prolongs phospholipid-dependent coagulation reactions; ∴ ↑
PTT
that does
not
correct with mixing study but does correct with excess phospholipids or platelets; PT not affected b/c the reaction contains much more phospholipid

β
₂
-GP-I:  Ab against β
₂
-glycoprotein-I, IgG or IgM

False
VDRL: nontreponemal test for syphilis in which cardiolipin is part of Ag complex

Clinical significance of different Abs in pathogenesis uncertain

Risk of thromboembolic phenomena may increase with titer of APLs

• Etiologies: primary (idiopathic) or secondary due to
autoimmune syndromes
(eg, SLE),
malignancy
,
infections
, drug reactions • Treatment: UFH/LMWH → warfarin after thromboembolic event (lifelong for most Pts)

Intensity of anticoagulation controversial (
Arthritis Rheum
2007;57:1487)

Initial
venous thrombosis
: INR 2–3 (
NEJM
2003;349:1133;   
J Thromb Haemost
2005;3:848)

Initial
arterial thrombosis
: typically INR 2–3 + ASA 81, although some treat to INR 3–4

Recurrent thrombosis
on warfarin: INR 3–4 vs. LMWH (
Arth Rheum
2007;57:1487)

Consider ASA prophylaxis for high-risk asx Pt (eg, SLE)

DISORDERS OF LEUKOCYTES