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(Editor's Note: This is the second part of a two-part series. Click here to view Part 1)

Thrombophilia and Pregnancy
Utilization of anticoagulation to prevent pregnancy complication is becoming more frequent in patients with hereditary thrombophilia. Combination therapy with aspirin also is used for the prevention of recurrent pregnancy loss in women with antiphospholipid antibodies. Treating pregnant patients with anticoagulation is challenging because of both maternal and fetal complications.⁶

Consideration must be given to the frequency, type of administration, side effects and risks and benefits of therapy in pregnancy. Harmful effects, including maternal bleeding, congenital malformations and burden of treatment, must be compared with the benefits of avoiding VTE or pregnancy loss.⁶

Directives in this document include:

• "For women receiving anticoagulation for the treatment of VTE who become pregnant, we recommend LMWH over vitamin K antagonists during the first trimester (Grade 1A), in the second and third trimesters (Grade 1B), and during late pregnancy when delivery is imminent (Grade 1A)."⁶
• "For pregnant women with no prior history of VTE who are known to be homozygous for factor V Leiden or the prothrombin 20210A mutation and who do not have a positive family history for VTE, we suggest antepartum clinical vigilance and postpartum prophylaxis for 6 weeks with prophylactic- or intermediate dose LMWH or vitamin K antagonists targetedat INR 2.0 to 3.0 rather than routine care (Grade 2B)."⁵
• "For women with two or more miscarriages but without APLA or thrombophilia, we recommend against antithrombotic prophylaxis (Grade 1B)."⁵
• For lactating women using LMWH, danaparoid, or r-hirudin who wish to breast-feed, we recommend continuing the use of LMWH, danaparoid, or r-hirudin (Grade 1B).

New Antithrombotic Drugs
New antithrombotic drugs have been developed to provide better therapeutics without the limitations of existing anticoagulants. Most advances have occurred in the area of antiplatelet drugs and anticoagulants. Advances in fibrinolytic drugs have lagged.⁷

Antiplatelet agents include targets of thromboxane A2, ADP or thrombin receptors on platelets. ADP receptor antagonists, like clopidogrel, target P2Y 12, whereas the thrombin receptor antagonists target PAR-1.7

The mechanism of anticoagulation can be achieved by several routes. Initiation is blocked by drugs that target the tissue factor/factor VIIa complex. Propagation of coagulation is blocked by drugs that inhibit factor IXa or factor Xa, or their cofactors, factor VIIIa and factor Va. Other anticoagulants that target thrombin attenuate fibrin generation. These can be further subclassified as direct or indirect inhibitors. Direct inhibitors bind directly to the target enzyme and block substrate interactions, while indirect inhibitors bind to naturally occurring plasma cofactors, such as antithrombin or heparin cofactor II, accelerating their interaction with clotting enzymes.⁷

A better understanding of fibrinolysis has led to the development of new agents. This includes methods to enhance endogenous fibrinolysis that include inhibitors of type 1 plasminogen activator (PAI-1), urokinase plasminogen activator (u-PA), TAFIa, or activated factor XIII (factor XIIIa). New fibrinolytic agents include alfi meprase, V10153, plasmin and desmoteplase.⁷

Innovations in ACCP's 9th Edition of 'Antithrombotic Therapy and Prevention of Thrombosis'
ACCP guidelines contain evidence-based information that has been graded to enhance the quality and relevance of recommendations. Major innovations include:

1. Unconflicted methodologists as topic editors. Conflicted experts did not participate in final process of making recommendations.
2. Many evidence profile and summary of finding tables.
3. New insights into evidence (asymptomatic thrombosis, aspirin).
4. Quantitative specification of values and preferences based on systematic review of relevant evidence and formal preference rating exercise.
5. Article addressing diagnosis of DVT.¹

Donna D. Castellone is clinical science manager, Roche Diagnostics.

References

1. D. Gutterman., D. Zelman Lewis, S., Guyatt, GH., Akl, EA., Crowther, M, Schünemann, HJ., Guttermann, DD, Introduction to the Ninth Edition: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest 2012;141; 48S-52S
2. Gordon, G., Gutterman, D., Baumann, MH., Addrizo-Harris, D., Hylek, EM., Philips, B., Raskob, G., Lewis, SZ., Hshuemann, H., Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines, Chest, 129: 2006, 1174-181.
3. Eikelboom , JW., Hirsh, J., Spencer, FA, Baglin , TP ,Weitz, J , Antiplatelet Drugs Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, CHEST 2012; 141(2)(Suppl):e89S-e119S
4. Guyatt,GH, Akl, EA, Crowther, M., Gutterman, DD., Schuünemann, HJ., Executive Summary : AntithromboticTherapy and Prevention of Thrombosis, 9th Clinical Practice Guidelines ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 2012;141;7S-47S
5. Hylek, EM, Palareti, G., Ageno, W., Gallus, AS, Wittkowsky,A, Crowther, M., Oral Anticoagulant Therapy: Antithrombotic Evidence-Based Clinical Practice Guidelines: American College of Chest Physicians Therapy and Prevention of Thrombosis, 9th ed Chest 2012;141;e44S-e88S.