Medication Summary

Management of patients with recurrent miscarriage due to hemorrhagic disorders is generally with plasma substitution therapy or, in appropriate disorders, DDAVP (vasopressin) therapy.^{[1, 4]}Treatment of patients with thrombotic disorders is with aspirin, heparin, or low-molecular weight heparin (LMWH).

Aspirin

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Antiplatelet effect indicated to decrease risk of thrombosis and pregnancy loss in pregnant women with antiphospholipid antibody (APS) syndrome. Although not proven effective when used alone, most clinicians use aspirin with subcutaneous heparin in pregnant patients with APS. Begin aspirin as soon as conception is attempted.

Inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate).

Heparin

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Indicated to decrease risk of thrombosis and pregnancy loss in pregnant women with APS.

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents re-accumulation of clot after spontaneous fibrinolysis.

Enoxaparin

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Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing.

LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared to UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE.

No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect).

Average duration of treatment is 7-14 d.

Indicated to decrease the risk of thrombosis and pregnancy loss in pregnant women with APS.

Dalteparin

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Enhances inhibition of Factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of Factor Xa.

Except in overdoses, no utility exists in checking PT or aPTT because aPTT does not correlate with anticoagulant effect of fractionated LMWH.

Average duration of treatment is 7-14 d.

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Defects causing recurrent miscarriage.
Dallas/Fort Worth Metroplex (DFW Metroplex) flow protocol.

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Table 1. Characteristics of the First 351 Women Referred for Hemostasis Evaluation

Patient Characteristics (All 351 Patients)	Mean	Standard Deviation	Maximum	Minimum
Age, y	33.3	5.63	49	18
Number of Miscarriages	2.9	2.39	9	2

Table 2. Clotting Disorders Found in the Authors' Population

Antiphospholipid Found	Patients With APLS, %
ACLA-IgG only	32.6
ACLA-IgM only	23.4
ACLA-IgA only	7
ACLA-IgG + IgM	3
ACLA-IgG + IgA	1
ACLA IgA + IgM	0
Lupus anticoagulant only	2
ACLA + lupus anticoagulant	2
Subgroup Only (No ACLA or lupus anticoagulant present)
Antiphosphatidylserine	4
Antiphosphatidylinositol	2
Antiphosphatidylethanolamine	5
Antiphosphatidic acid	5
Antiphosphatidylcholine	7
Antiphosphatidylglycerol	1
Anti-annexin-V	5
B2GP1	0
Hexagonal phospholipid	0
Total
(9 Patients had ACLA + a subgroup antibody)
Total with only a subgroup antibody
APLS patients with only a subgroup antibody, %	29