Blood Hematopoietic Disease :Thrombopenia and Platelet Dysfunction

• Disease which becomes easy for bleeding caused by the reduction of blood platelet.
• There are 3 causes like the decrease in platelet production capacity.
• In case of being severe condition, there is a risk of bleeding in the skull.
• To diagnose, correct count of blood platelet is inevitable.
• Administrate immune suppressor for frequent acute ITP.

Disease which becomes easy for bleeding caused by the reduction of blood platelet.

Blood platelet is one of the blood integrant appeared in peripheral blood which is produced in bone-marrow as same as red blood cell or leucocyte. In case of blood vessel wall is damaged, platelet gathers at the wound site and is hemagglutinated to prevent bleeding to perform the function of arresting hemorrhage. When amount of platelet is reduced too much tendency of bleeding becomes high. On the contrary, even though the amount of platelet is normal, in case if the work (function) shows its abnormality, tendency for bleeding also getting high. On the other hand, when amount of platelet becomes too much, it becomes easy to develop thrombosis and leads to cardiac infarct or brain infarct.

Thrombocytopenia is meant to be in the stage of reduced platelet, and platelet dysfunction is meant the hereditary platelet function abnormalities. Also, when diagnosing thrombocytopenia, differentiation of platelet size (whether it is a giant platelet larger than normal one or micro platelet smaller than the normal.

There are 3 causes like the decrease in platelet production capacity.

There are 3 causes for thrombocytopenia. Roughly speaking, they are; production capacity at bone-marrow is reduced, increased platelet usage or destruction at the peripheral blood, platelet distribution abnormalities at internal organs. In congenital (inherited) platelet dysfunction, there are with reduced platelet count type and without reduced platelet count type.

The decrease of pan-blood cells by bone-marrow failure

There is the case where disorder, such as aplastic anemia or acute leukemia, appears in all 3 blood cell systems, and the case where Congenital non-spherical thrombocytopenia becomes an issue as the disorder limited to the platelet producing megakaryocyte.

Thrombocytopenia due to the decrease in platelet life caused by destruction of platelet.

Idiopathic thrombocytopenic purpura (ITP) is the most frequently appeared disease in thrombocytopenia. The order of their own immunology is assumed, but the most common one is by virus infection, and there is a case where the disease can be seen in collagenosis related, or there is a case with helicobacter pylori infection.

Thrombocytopenia by the increase of platelet consumption

This can be seen on disseminated intravascular coagulation syndrome (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic-uremic syndrome (HUS).

Drug-induced thrombopenia

Heparin-induced thrombocytopenia (HIT) is the most commonly known. In this disease, there are type I developed by non-immunological mechanism, and type II in which Heparin dependent autoantibody appears.

Thrombopenia by platelet distribution abnormality in internal organs.

This can be seen at hypersplenism complicated with bone-marrow fibrosis, vascular storage (Kasabach-Merrit syndrome) of platelet by giant hemangioma.

In inherited platelet dysfunction, as mentioned below, there are with or without the reduction of platelet count, and in large platelet size or small size one.

• Platelet stress disorder (indicate abnormality at platelet agglutination but platelet count is normal)
• Bernard Surie syndrome (Abnormality in platelet adhesion, mild reduction in platelet count)
• MYH9 Disorder (platelet size is large, and characterized by macro-thrombocytopenia; May Hegglin syndrome, Epstein syndrome
• Wiskott Aldrich syndrome (WAS) (there is platelet count reduction, platelet size is small, and characterized by micro-thrombocytopenia.

In case of being severe condition, there is a risk of bleeding in the skull.

As a symptom, bleeding from skin or mucosal are common. In case there is an abnormal blue spot or dot hemorrhage, thrombopenia is suspicious. Generally speaking, count of platelet normally are between 150k to 350k/µL, so that if it decreases down to 80k to 100k/µL, bleeding spot may appear by light bruise, and less 50k/µL, bleeding spot appears more easily., and further in case it goes down to 10k/µL or less, dot hemorrhage may occur. Clinically speaking, platelet infusion of administration of platelet count increasing drug becomes necessary because of the risk of bleeding in the skull is getting high when count of platelet exceeds more than 20k/µL.

To diagnose, correct count of blood platelet is inevitable.

Idiopathic thrombocytopenic purpura (ITP) is separated into acute type and chronic type. In chronic ITP, there is the case where it may transit to aplastic anemia or chronic myelodysplastic syndrome (MDS) at later stage. Inherited disease will usually take chronic process.

For examination and diagnosis, accurate count of platelet is necessary. There is an issue of false platelet reduction, and this is meant that platelet shows smaller count than actual count due to several causes. Well known false platelet reduction is caused by anticoagulant EDTA. In the diagnosis of ITP, examination of PAIｇG (measure IgG antibody combined with platelet) or antiplatelet antibody (there are autoantibody and antiplatelet type antibodies which are seen on ITP), and bone-marrow examination can also be referred. In ITP, megakaryocyte count in bone-marrow is normal or increasing, matured megakaryocyte indicating platelet production is less, and young megakaryocyte which is unable to produce platelet becomes as main. (fig.1)

In case platelet dysfunction is suspicious, platelet surface antigen (CD41, CD42a, CD42b, CD61) is checked by flow cytometry using platelet floating plasma (PRP). There is a case where bone-marrow examination is conducted to search the cause of platelet reduction.

Administrate immune suppressor for frequent acute ITP.

Treatment is corresponded with the causes. For the most frequent acute ITP, steroid, immune globulin (IVIG), Rituxan for intractable case, are used. There is the case where splenectomy becomes adaptable or pylorus eradication becomes effective. Recently, LeboradeTM (oral medicine) which is a thrombopoietin receptor agonist for chronic ITP and RomiplateTM (hypodermic injection) becomes subject to the health insurance.

Diagnose of inherited platelet reduction/platelet dysfunction should be performed adequately, and in the diagnosis defined case, careful follow-up is necessary to prepare symptom like bleeding or else occurrence. There is a case where platelet transfusion is requested, but it is necessary to correspond with checking whether anti-platelet type antibodies is positive or not in the platelet transfusion refractory state which does not react even platelet is transfused.

Fig.1 (A) megakaryocyte actively producing platelet, (B) young megakaryocyte unable to produce platelet at ITP.