Prothrombotic bleeding disorders

What is it?

When an artery, vein, or capillary is injured or ruptured, a system is activated to plug the blood leak (wound). This process is called. Once the bleeding has stabilized, the fibrinolysis system is activated, a mechanism that allows the clot that has been created to be undone when it is no longer necessary.

If there is a disorder, either in platelets, or in coagulation factors, either due to quantitative excess or qualitative alterations, hemostasis and coagulation will occur in an excessive way, so there will be an ease for disorders to occur thrombotic.

Two phases

Haemostasis consists of two phases:

How is it produced?

Prothrombotic disorders can have their origin in two large groups of causes:

• Primary or essential, a myeloproliferative syndrome of the bone marrow.
• Secondary or reactive to any disease.

• Leiden factor V.
• Hyperhomocysteinemia.
• Protein C deficiency.
• Protein S deficiency.
• Antithrombin deficiency.
• Alteration of plasminogen.
• Antiphospholipid syndrome.
• Disseminated vascular coagulation (DIC).

Essential thrombocytosis is due to excessive proliferation in the bone marrow of megakaryocytes, the precursors of platelets. As in all, the other cell lines also reproduce in greater numbers than usual, but the predominant line is that of platelets.

Secondary or reactive thrombocytosis is much more common than primary. The main cause of secondary thrombocytosis is usually iron deficiency, that is, iron deficiency, so that this is often solved with oral administration of iron supplements, so that correcting iron levels restores the normal number platelets.

Other pathologies that can cause secondary thrombocytosis and that must be ruled out are severe acute infections, chronic inflammatory diseases, neoplasms, treatment with chemotherapy, the use of folic acid or vitamin B12, or some drugs.

The vast majority of clotting factor disorders are autosomal dominant, the most common being factor V Leiden, which consists of resistance to protein C, which is responsible for inhibiting activated factor V, so that Coagulation cascade does not stop and predisposes to clotting.

The deficiency of protein C and protein S, despite being most of the time of hereditary origin, can be secondary to severe liver disease, chemotherapy treatment, serious infections, pregnancy or. Similarly, antithrombin deficiency can also be secondary to nephrotic syndrome, treatment with heparin, estrogens (such as oral contraceptives), or severe liver disease.

Antiphospholipid syndrome is an autoimmune disorder that causes both thromboembolism and a decrease in the number of platelets.

In disseminated vascular coagulation (DIC), due to severe generalized infections, certain tumors, autoimmune diseases or severe trauma, excess coagulation and thrombi initially occur, although as platelets and clotting factors are depleted, bleeding occurs in phases. advanced.

Symptoms

The symptoms of excess coagulation are thrombosis or thromboembolism, both in arteries and veins. They are frequent, especially at the level of the lower extremities. When a thrombosis occurs there is pain in the affected area, filling, redness and an increase in temperature. Depending on the area in which the thrombosis occurs, the symptoms will be one or the other, and there may even be heart or brain involvement.

In the case of primary thrombocytosis, the involvement is mainly neurological, although erythromelalgia, which consists of burning pain in both hands and feet, or priapism, a painful and irreversible erection, is also characteristic. Splenomegaly occurs in less than 20% of cases, and occasionally there may be hemorrhagic phenomena.

Treatment

Treatment will depend on the factor causing the thrombosis. In the case of iron deficiency, oral iron intake for three months is usually sufficient to restore normal platelet values. Likewise, the correct treatment of infections or inflammatory diseases that can cause an increase in the number of platelets is usually enough to normalize their numbers and avoid thromboembolic processes.

In case of presenting essential thrombocytosis, the treatment would be bone marrow transplantation if the patient is a candidate for it. If this is not possible, palliative treatments with chemotherapy and transfusions will be given.

Clotting factor disorders can be tried to alleviate with the use of anticoagulant drugs, such as heparin or acenocoumarol (Sintrom®). These treatments must always be prescribed by the hematologist and require close monitoring of the patient.

Diagnosis

The diagnosis will be suspected as a result of either the presence of one or more episodes of thrombosis or the accidental finding of some laboratory abnormality. A correct examination of the patient must be carried out in search of possible signs of thrombosis or embolisms, as well as the use of medications for any other pathology. It is important to collect a family history to discover a possible inherited bleeding disorder.

A complete analysis must be performed to assess the number of platelets and the main clotting factors, as well as the levels of iron, ferritin, transferrin, vitamin B12 and folic acid to rule out iron deficiency as the main house of secondary thrombocytosis. One must speak of a thrombocytosis when a figure of more than 600,000 platelets / mm3 is found. Similarly, parameters of infection or chronic inflammation, such as ESR, C-reactive protein, rheumatoid factor, and other antibodies should be assessed.

If secondary thrombocytosis is ruled out and a primary one is suspected, a hematologist should be consulted to carry out the pertinent studies, including if necessary a bone marrow aspirate.

Precautionary measures

There are no preventive measures for most bleeding disorders, but one can try to avoid risk factors, such as estrogenic oral contraceptives in patients with inherited bleeding disorders or poor peripheral venous circulation. In the presence of thrombotic phenomena, it is essential to put yourself in the hands of the specialist as soon as possible.

• When a thrombosis occurs there is pain in the affected area, filling, redness and an increase in temperature.
• Estrogenic oral contraceptives in patients with hereditary coagulation disorders or poor peripheral venous circulation are a risk factor that should be avoided.
• Treatment will depend on the factor causing the thrombosis.