Polymorphism of hemostasis genes

The identification of polymorphisms of hemostasis genes is currently one of the main passions of both patients and doctors. Our love for these fancy letters is characterized by the prescription of thrombophilic mutation investigations for which there are no indications and that are thrombogenically insignificant; by excessively frequent investigations of the hemostatic system and LMWH dose adjustment based on D-dimer values, the equation of uteroplacental blood flow hemostasis with the peripheral bed hemostasis. We do not always understand the difference between hypercoagulation and thrombophilia
The analysis may well be prescribed, but only to some patients and only in certain clinical situations.
It makes sense to identify the following:

1. Factor V (Leiden) mutation – a homozygous mutation;
   
2. Protein C and S deficiency, antithrombin deficiency;
   
3. Factor II (prothrombin) mutation - a homozygous mutation;
   
4. A combination of the heterozygous Leiden 5 and G20210A mutations.

It has been proved that miscarriages in the second trimester and the carriage of Leiden, factor II and protein S mutations are connected.

There are scales for risk assessment as well as for the choice between prophylactic and therapeutic LMWH doses.

In case a patient scores 1 point, preventive LMWH doses are recommended during the whole period of pregnancy and for 6 weeks after the delivery. If a patient scores 2 points or more, therapeutic LMWH doses are indicated for the same period of time.


It makes sense to prescribe these investigations in the following cases:

• Medical history of venous thromboembolic complications;
  
• Venous thromboembolic complications in first-degree relatives;
  
• Fetal loss after 10 weeks of pregnancy;
  
• Severe fetal growth retardation or placental insufficiency;
  
• Recurrent miscarriages;
  
• Severe pre-eclampsia, HELLP syndrome;
  
• Placental abruption.

The use of LMWH therapy can improve pregnancy results in patients with recurrent miscarriages in the second trimester as well as with the carriage of one or several of the above-mentioned mutations. However, the same therapy conducted in the first trimester did not show any significant effect.

It is the only "purely" obstetric planned indication for LMWH. There are no evidence-based studies telling us about the need for LMWH "preconception preparation" prior to IVF, during IVF, over the whole period of pregnancy and further on as long as you can keep going.

Here are the cases when patients actually need thromboprophylaxis in the IVF programme:

1. Medical history of an episode of deep venous thrombosis;
   
2. Ovarian hyperstimulation syndrome with the need for hospitalization (the risk of thrombosis increases 100-fold);
   
3. Proven antithrombin deficiency;
   
4. A combination of age >40 and/or smoking and APS or carriage of the above-mentioned polymorphisms;
   
5. Multiple risks: obesity + low physical activity + smoking; but still we included the patient into the IVF programme.

If we exclude the 5^th article (we are doctors after all, not reapers), we will see that LMWH will be needed only by a very small number of patients in the protocol. The preventive and the therapeutic LMWH doses are adjusted based on a patient's weight; and they are but approximate. Hemostasis values that are subject to control are also clearly specified: APTT, PI (INR), fibrinogen, platelet concentration. The list in high-risk groups additionally includes TEG and D-dimer values. One should bear in mind that the implantation process and the whole period of pregnancy are normally accompanied by physiological hypercoagulation that is by no means to be contended with.

All other patients taking expensive LMWH medication and administering abdominal injections for weeks do not help themselves at all. Perhaps, they even harm themselves...