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At last it has happened. You have succeeded in getting pregnant, and all tests show that the pregnancy is good. There is an embryo implanted in the endometrium of your uterus, and there is a heartbeat, a good strong heartbeat, which you heard yourself during an ultrasound exam. But it happens that you also have an “inherited platelet disorder” – a medical condition that causes you to bleed more than you should, due to an inherited problem with platelets, also known as thrombocytes. They’re not cells exactly, but cell-like entities that circulate in the blood and are packed with various chemicals that are needed for clot formation, the process that stops bleeding. Chemicals released from platelets work in concert with various proteins, called clotting factors, or coagulation factors, that are located in the blood or in the cells that line the insides of blood vessels. In the process of clot formation, platelets aggregate; they stick together, forming a plug to help with blood vessel healing. That’s all well and good when it works, but blood clotting is a phenomenon that could have fit perfectly into the old story of Goldilocks and the three bears, since it depends on a range conditions being just right –not too far to one extreme or the other.
Remember, how Goldilocks finds one bowl of porridge that’s too hot and another that’s too cold, a bed that’s too hard and another that’s too soft. Only when she tries the porridge of an intermediate temperature she is satisfied. The same is true when she finds the bed that is neither too soft nor too hard. But, did you know that a similar thing happens with your body’s coagulation system? Too much of a tendency to clot blood causes trouble; clots, or thrombi, form in veins, in structures called venous sinuses, and even in certain parts of the heart. This can produce an embolus, a traveling clot that soon obstructs a blood vessel in the lungs, the brain, or another organ, thus interfering with blood supply to the tissue that the vessel serves, leading to ischemia, an inadequate supply of oxygen and other needed supplies. If this goes on, in can lead to infarction, death of tissue. Not enough tendency to clot, however, means that you have a tendency to bleed, that there is a risk of hemorrhage, even from something that does not normally cause a bleed. Only when coagulation system is balanced in a kind of “Goldilocks zone”, are the risks of blood vessel obstruction and hemorrhage both reduced to a minimum.
If you have platelet disorder, the balance is off; you are not in the coagulation “Goldilocks zone”. You are into the bleeding end of the spectrum. This can coexist with pregnancy.
So, what do platelets do and how are they affected by inherited disorders? Platelet function depends on the presence of certain proteins on the surface of the membrane that surrounds the platelet. These proteins help attach the membrane of the platelet to other platelets and to certain clotting factors made outside the platelet. Platelet function also relies on granules (packages) of chemicals that are stored inside the platelet and released during the clotting process. Manufacture of the granules and their contents and platelet surface proteins all depend on genes that you inherit from your parents. Consequently, platelets are vulnerable to abnormalities in the genetic information. Any mistakes can result in problems in the body’s ability to form clots. Sometimes, the changes in hormones and blood during pregnancy can exacerbate the problems resulting from genetic abnormalities.
There are numerous categories of inherited platelet disorders. Here, we’ll name just a few, not to inundate you with information, but just to give you an idea of the many things that can go wrong. Some people suffer genetic problems involving the granules inside the platelets, called storage pool disorders. Others suffer platelet surface protein abnormalities. One such disorder, called Glanzmann thrombasthenia, results from a problem with a complex of surface proteins called glycoprotein IIb-IIIa. Another inherited surface protein disorder is called Bernard-Soulier syndrome, which is a problem with a surface protein called glycoprotein Ib. The role of this protein is to bind with a very large protein called von Willebrand factor (vWF), which is also produced in platelets.
Problems with vWF itself constitute what hematologists call von Willebrand disease (vWD). Although vWD is the most common inherited bleeding disorder, platelets are not the only source of vWF, so vWD is not really categorized as a platelet disorder like the other conditions that we have mentioned. In contrast, Bernard-Soulier syndrome, Glanzmann thrombasthenia, and storage pool disorders, though much less common than von Willebrand disease, are particularly challenging to manage in pregnancy.
Treatment of these conditions depends greatly on medications, such as the clotting factor thrombin to stop bleeding. Essentially, thrombin that is given as a medication is genetically engineered clotting factor called recombinant factor VIIa, which is safe if you are pregnant or nursing. Another treatment is physicians call antifibrinolytic therapy, which consists of a drug called tranexamic acid, which is considered to be safe both during pregnancy and when you are nursing. Most important of all the treatments is infusion of platelets into your blood, in the event that symptoms reach a certain level of severity (indicated by your platelets being below a certain level when your blood samples are sent to the lab).
As for long-term treatment, there is a therapy that actually cures the condition, namely hematopoietic stem cell transplant. This is not something that you can receive during pregnancy, but it is an option prior to becoming pregnant, or after. Finally, on the horizon there is gene therapy, which also stands to cure the conditions.
