Immune (Idiopathic) Thrombocytopenic Purpura

Primary immune thrombocytopenia (ITP), commonly known as idiopathic thrombocytopenic purpura, is an inflammatory bleeding disorder that affects both adults and infants. Until quite recently, it was considered an autoantibody disorder in which the reticuloendothelial system prematurely removed platelets, which were opsonized with antiplatelet antibody. More recently, findings have shown that there is a significant underproduction of platelets in certain cases, which leads to the thrombocytopenia found in this disease.

Many people have no health conditions but there may be bleeding. In its clinical course ITP is impredictable. To date, treatment has been aimed at reducing the destruction of platelets mainly through immunosuppression. Nonetheless, modern agonists of thrombopoietin receptors have been produced to increase the development of platelets for the bone marrow. Those modern tailored drugs are expected to be correlated with less risk than conventional therapy owing to immunosuppression.

Clinical features

The two principal forms of ITP,  are quite distinct in their underlying cause and presentation.

Acute ITP

This is mainly a children’s disease, but an occasional related syndrome is seen in adults. The disease is defined in a normally stable infant by the sudden appearance of swelling, petechiae, and occasionally mucosal bleeding (e.g., epistaxis). The predominant hematologic symptom is thrombocytopenia, which mostly develops 1 to 3 weeks following an infection.

Very commonly, the outbreak is a non-specific upper respiratory tract or viral infection of the gastrointestinal tract, although acute ITP can often arise with rubella, rubeola, chickenpox or other viral diseases, which can accompany live vaccination of virus. Acute ITP prevalence is reported to be 4 in 100,000 babies, with a peak occurrence in children aged between 2 and 5 years. There is no predisposition over sex. In around 10 to 15 percent of children who originally believed they had acute ITP, thrombocytopenia continues for 6 months or more, and these children are reclassified as having persistent ITPs. The discovery that acute ITP frequently accompanies a viral disease indicates that certain children develop antibodies and immune complexes against viral antigens, and that the destruction of platelets can result from attaching these antibodies or immune complexes to the platelet surface.

Most patients with acute ITP recover in around 3 weeks with or without care, but it can take 6 months for others to heal. Recurring cases of severe ITP are rarely seen in a number of kids following complete recovery from the first episode. Most patients with acute ITP have fairly minor signs and require no care. However, the more serious cases may continue to be handled, so the most urgent advantage tends to be intravenous immunoglobulin (IVIG), platelet transfusions, so splenectomy (or any variation of them).

Chronic ITP

This condition can be seen in patients of any generation, but the majority of cases arise in patients aged 20 to 50 years. Females with this disease outnumber males 2:1 to 3:1, with the greatest prevalence of females between the ages of 20 and 40. Chronic ITP typically continues insidiously, with platelet counts reducing variable and often regular for stretches of time. Symptoms present include signs with mucocutaneous bleeding, with the most frequent being menorrhagia, recurrent epistaxis and simple swelling (ecchymosis).

The degradation of platelets in chronic ITP is the result of an immunological cycle. The guilty antibodies bind to platelets, and as a consequence reticuloendothelial cells, mainly in the spleen, expel the antibody-labeled platelets from circulation. Autoantibodies that recognise platelet surface glycoproteins such as glycoprotein IIb (GP IIb) and GP IIIa (aIIb/b3), GP Ia/IIa, and others can be seen in 50 to 60 percent of patients with ITP. These cells are clear targets of the antibodies since megakaryocytes often produce GP IIb / IIIa and GP Ib / IX on their membranes. Studies of the platelet turnover demonstrated reduced platelet development at ITP. Overall, the platelet’s life cycle is reduced from average 7 to 10 days to a few hours, and the level at which platelets are eliminated from circulation is associated with the degree of thrombocytopenia.

If plasma from an ITP patient is infused into a normal recipient’s circulation, thrombocytopenia develops for the recipient. The ITP patient’s plasma-producing agent for thrombocytopenia is an immunoglobulin G (IgG) antibody which can be extracted from the serum by adsorption of regular human platelets. In addition, cytotoxic T cell-mediated platelet lysis was seen in vitro utilizing CD3, CD8 lymphocytes from active chronic ITP patients, but the in vivo relevance of this process is not established.

Clinical picture of Acute and Chronic ITP

Immunologic Drug-Induced Thrombocytopenia

Many medications may cause thrombocytopenia which is severe. Drug-induced immune-mediated thrombocytopenia can be classified into many groups, depending on the medication and platelet activity of the antibody.

Drug-dependent antibodies: Chinidine- and quinine-induced thrombocytopenia exemplifies one mechanism of drug dependent antibodies. The antibody caused by these medications associates with platelets even while the medication is active. Usually opioid based antibodies develop after 1 to 2 weeks of introduction to a new medication. Many drugs may induce such antibodies but derivatives of quinine, quinidine, and sulfonamide do so more frequently than other drugs. When antibody development has begun, the count of platelets decreases quickly and can always be less than 10,000 / μL. Patients can have bleeding signs suddenly on. If this form of thrombocytopenia caused by the medication occurs in a pregnant woman, it may influence both her fetus and she.

Common Drugs Causing Immune Thrombocytopenia

Analgesics

Salicylates
Acetaminophen
Phenylbutazone
AntibioticsCephalothin
Penicillin
Streptomycin
Aminosalicylic acid
Rifampin
Novobiocin
Various sulfa drugs (chlorthalidone, furosemide)
AlkaloidsQuinidine
Quinine
Sedatives, AnticonvulsantsMethoin
Troxidone
Chlorpromazine
Diphenylhydantoin
Meprobamate
Phenobarbital
Carbamazepine
Oral HypoglycemicsChlorpropamide
Tolbutamide
Heavy Metals

Gold
Mercury
Bismuth
Organic arsenicals
Miscellaneous

Chloroquine
Chlorothiazide
Insecticides


Hapten-induced antibodies:
A second type of hapten dependent antibodies is development of thrombocytopenia caused by the medication. Any drug molecules are too tiny on their own to cause an immune reaction but they may function as a hapten and interact with a larger carrier molecule (usually a platelet membrane plasma protein or protein constituent) to create a complex that can serve as a full antigen. This form of thrombocytopenia caused by the medication is always serious. The original count of platelets can be fewer than 10,000 / mL, although at times less than 1000 / mL. The amount of megakaryocytes in the bone marrow is usually usual to elevated.

Drug-induced autoantibodies: Drug-mediated autoantibodies are a third cause of the thrombocytopenia caused by the medication. In this situation, the drugs induce autoantibody formation that binds to a particular platelet membrane glycoprotein with no prerequisite for free drug presence. Two sources of these medicines are the gold salts and procainamide.

Immunoglobulin binds a platelet membrane antigen or antigen and drug combination. Macrophage Fc receptors bind the Fc portion of the Immunoglobulin. This may result in platelet removal and Thrombocytopenia.

Immune complex–induced thrombocytopenia: Heparinduced thrombocytopenia (HIT) represents a good example of another type of thrombocytopenia induced by the drug. Heparin binds to platelet factor 4 (PF4), a protein shaped and released by platelets that neutralizes heparin. Heparin attachment by PF4 plasma or PF4 platelet membrane – expressed PF4 induces a conformational shift in PF4, resulting in neoepitope presentation. Exposure of such neoepitopes (“new antigens”) activates certain individuals’ immune response, contributing to the formation of an antibody at one of the neoepitopes. In HIT, heparin and PF4 form a complex on the platelet surface or circulating free complexes to which the antibody binds. The Fab portion of the immunoglobulin molecule binds to an exposed neoepitope in the PF4 molecule; this leaves the Fc portion of the IgG free to bind with the platelet FcγIIa receptor, which causes platelet activation.

The role of Helicobacter pylori in the development of ITP

A number of studies have shown improvement in platelet counts in ITP patients positive for H. Pylori, after bacterial eradication. The findings from various experiments are contradictory, though, with some centers having a very strong response rate to eradication while others have a weak response rate. Additional help may include H. Pylori in ITP derives from experiments that have demonstrated that the amount of antiplatelet antibodies in plasma reduces after bacterial eradication.

T cells may also be involved

The role of T cells in ITP ‘s growth is becoming more apparent. Since the autoantibodies in ITP are predominantly of the IgG subclass, that T cells are involved has been known for some time, and isotype switching from IgM to IgG requires T-cell help. Around 40 per cent of persistent ITP cases, though, do not have observable autoantibodies and are thrombocytopenic and appear to have real ITP. CD8 + T cells have been related to pathogenesis of multiple autoimmune disorders, such as type 1 diabetes, and it has been shown recently that ITP patients have a strong CD8 + T cell-a mediated cytotoxicity that causes platelet loss. At present, however, it is unknown whether cell – mediated platelet destruction contributes to the severity of disease or to the difficulty of treatment in some patients with ITP.

References:

  1. Rodaks Hematology 5th Edition
  2. Post Graduate Hematology 6th Edition
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