Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency

Figures & data

Figure 1 Antithrombin is inhibitory primarily to factors IIa (thrombin) and Xa as well as, to a lesser extent, to factors IXa, XIa, XIIa, and VIIa/TF.

Table 1 Details of treatment of six antithrombin (AT)-deficient pregnant patients

Case	Age, years	Parity	Basis for diagnosis	Indication for treatment with AT during pregnancy	Plasma AT level prior to initial AT treatment (%)	Treatment in pregnancy	Weeks’ gestation	Mode of delivery	Summary of procedures or AT concentrate for delivery
1	17	0	Strong family history of DVT	DVT R leg and PE at 20 weeks’ gestation	59	IVC ligation, IV and sc heparin	Term	Cesarean	Admitted at full-term for delivery. Given 50 units/kg loading dose. repeated 72 h later. Heparin discontinued and cesarean performed. 25 units/kg daily × 7 days thereafter. Heparin restarted 2 days PP. Coumadin started 4 days PP. Nadir AT levels prior to dosing were all approximately 80%. Discharged on Coumadin® (Bristol-Myers Squibb, New York, NY, USA)
2	18	0	DVT early pregnancy (also with strong family history)	DVT early pregnancy	38 at time of diagnosis	sc heparin	Term	Vaginal	Admitted in early labor with preeclampsia. 4 units FFP on admission, AT level still only 48%. Given AT 46 units/kg loading dose. Maintenance of 34 units/kg × 24 hours then 23 units/kg daily × 5 days. AT levels 64%–122%
3	23	0	Strong family history	Massive DVT L leg at 8 weeks’ gestation	50	IV heparin plus AT 54 units/kg loading dose, then 31 units/kg (60% of loading dose) ×3 days, followed by 54 units/kg twice weekly plus sc heparin. Then sc heparin plus AT concentrate increased to 72–76 units/kg twice weekly to maintain nadir plasma AT levels > 70%	Term	Vaginal	Coumadin PP
4	27	0	Strong family history	PE at 12 weeks’ gestation	50	2 units of FFP on admission. IV heparin plus AT 50 units/kg loading dose, then 33–50 units/kg × 10 days. Then AT 40–66 units/kg twice weekly for 1 more month with sc heparin. Plasma nadir AT levels remained > 66%. AT was discontinued for 1 month and resumed at 62 units/kg once weekly with sc heparin	Term	Vaginal	AT 62 units/kg increased to twice weekly in the 4 weeks prior to delivery. Coumadin PP
5	28	0	DVT age 20. Diagnosed after miscarriage on Coumadin	DVT R leg 8 weeks’ gestation	18 at time of diagnosis	FFP on admission. AT level still only 30%–46%. AT 62 units/kg loading dose. Daily maintenance doses of 38–39 units/kg	9	Termination of pregnancy	Discharged on Coumadin
6	35	0	DVT and PE at age 23 and strong family history	PE 12 weeks’ gestation	42	IV heparin plus AT 58.5 units/kg daily × 3 days then 29.3 units/kg × 8 days, then 58.5 units × 1 day	13	Termination of pregnancy	Termination of pregnancy after 1 week of therapy. Discharged 4 days later on Coumadin

Abbreviations: DVT, deep vein thrombosis; FFP, fresh frozen plasma; IV, intravenous; IVC, inferior vena cava; L, left leg; PE, pulmonary embolism; PP, postpartum; R, right leg; sc, subcutaneous.

Table 2 Course and treatment during pregnancy of women with antithrombin (AT) deficiency

	Pregnancies, n	Hx VTE	Current VTE	Baseline AT levels	Antepartum prophylaxis	Recurrent VTE	Peripartum AT concentrate
Brandt^Citation32	2	1	–	50%, 65%	sc heparin	0	550 units
Hellgren et al^Citation16	9	2	–	39%–52%	sc heparin	1	2000–5000 units (average dose 41 units per kg [range 37–46]) per infusion to maintain AT levels of ≥80%
Michiels et al^Citation34	2	0	–	42%, 55%	Oral anticoagulants	0	3000 units (1 of 2)
Samson et al^Citation35	1	1	0	20%	sc heparin	0	3000 units loading dose (50 units per kg); 1500 units (25 units per kg) 48 h later, then doses adjusted and repeated every 48 h to maintain AT levels ≥ 80%
De Stefano^Citation36	4	2	1	“Around 50%”	sc heparin + oral anticoagulants	0	2500–3500 units
Menache et al^Citation27	5	2	1	29%–65%	–	0	5–6 daily infusions of 30.4 to 93.0 IU/kg
Blondel-Hill and Mant^Citation37	2	2	0	46%, 62%	sc heparin	1	6 units FFP (1 of 2)
Kario et al^Citation38	1	1	0	–	3000 units AT concentrate 3× per week starting at 34 weeks’ gestation	0
Yamada et al^Citation39	2	2	0	50%, 59%	6000 units AT concentrate (1) and heparin + 1500 units AT concentrate (1)	1
Grandone et al^Citation40	15	1/3 women		–	–	0	None
Tiede et al^Citation28	9	7	0	33%–58%			Loading dose 21–81 units per kg recombinant AT, maintenance infusions of 160–436 IU/kg/day × 3–10 days
Hidaka et al^Citation41	1	1	1	31%	sc heparin + 3000 units AT concentrate 2–3 × per week target ≥ 70%	1
Sabadell et al^Citation42	18	5/9 women	3 (untreated pregnancies)	33%–57%	12/18 with LMWH	0	“In labor”
Pamnani et al^Citation43	1	1	0	54%	LMWH	0	3091 units recombinant AT followed by 712 units per hour
Sharpe et al^Citation44	1	1	1	38%	LMWH + AT concentrate 2000–3000 units per day after sagittal vein thrombosis at 34 weeks		3000 units × 3 days at delivery then 2000–3000 units per day × 6 weeks
Kovac et al^Citation45	1	1	0	33%	LMWH	0	1 dose 50 units per kg

Abbreviations: Hx VTE, medical history of venous thromboembolism; LMWH, low-molecular-weight heparin; VTE, venous thromboembolism; sc, subcutaneous.

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