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Paroxysmal nocturnal hemoglobinuria: signs and symptoms

Most people with primary PNH have a red urine index at some stage of the disease, and many still have low red blood cell inactivation, which can lead to anemia

Signs and symptoms

Paroxysmal nocturnal hemoglobinuria: signs and symptoms

And then they show symptoms of anemia such as fatigue, shortness of breath, shortness of breath, and palpitations. 

Through the laboratory examination of the urine, it is possible to determine the results of the breakdown of red blood cells (hemoglobin and hemosiderin).

A small percentage of patient reports presented other symptoms such as abdominal pain, dysphagia, dysphagia, or dysphagia (pain during swallowing), as well as impotence in men - this mainly occurs when red blood cells are broken down rapidly.

Forty percent of patients develop thrombosis (blood clot) at some point in their disease. It is the leading cause of severe complications and death from PNH. 

They may develop in generalized sites (deep venous thrombosis in the foot, pulmonary embolism, and pulmonary embolism when these clots develop into the lungs), but, in PNH, 

clots may also form in more unusual sites in the hepatic vein (Budd-Chiari syndrome) and in the portal vein Portal to the liver (causing portal vein thrombosis), to the superior or inferior mesenteric vein (causing mesenteric ischemia), and to the skin veins. 

Cerebral venous thrombosis, the common name for which is ischemic stroke, is most common in paroxysmal nocturnal hemoglobinuria.

Diagnosis

The results of blood analysis in patients with paroxysmal nocturnal hemoglobinuria show symptoms consistent with intravascular hemolytic anemia such as low hemoglobin, lactate 

dehydrogenase, lactate dehydrogenase, and reticulocytes, effects of reticulocytes (immature red blood cells emanating from the bone marrow to replace destroyed cells), bilirubin effects, and bilirubin. 

(caused by the breakdown of hemoglobin), and a decrease in haptoglobin levels. The direct antiglobulin test (DAT, or what is known as the direct Coombs test) is negative because the hemolysis in paroxysmal nocturnal hemoglobinuria is not caused by the antibodies.

The glycolysis test, or sucrose, is used in patients whose red blood cells have been placed in a low-resistance ionic solution, and it is noted that the hemolysis process is used in the examination process. 

The more specific test for paroxysmal nocturnal hemoglobinuria, called the Hamm test for hemolysis (after Dr. Thomas Hamm, who described the test in 1937), the test is performed if the glucose test is positive for hemolysis. 

cite journal doi 10.1056/NEJM193712022172307 author Ham TH Chronic ha lytic ana ca with paroxysmal nocturnal ha myoglobinuria study of the mechanism of analysis in relation to 

acid-base equilibrium journal N Engl J Med year 1937 volume 217 pages 915–918 Flow cytometry includes flow cytometry of CD55 and CD59 on red blood cells, red blood cells, and white blood cells. 

Depending on the presence of these molecules on the cell surface, these methods are classified as type I, II, or paroxysmal nocturnal hemoglobinuria type III. In type 1, the cells 

have normal levels of CD55 and CD59; As for the second type, cells in it contain low levels, while the levels are absent for the presence of CD55 and CD59 in the third type. A high number of type 3 cells may lead to an increased risk of hemolysis and blood clotting.

Category

According to the diagnosis, paroxysmal nocturnal hemoglobinuria is classified into

• classical paroxysmal nocturnal hemoglobinuria. Evidence of PNH in the absence of a bone marrow disorder.

•Paroxysmal nocturnal hemoglobinuria to determine the status of another bone marrow disorder

• subclinical paroxysmal nocturnal hemoglobinuria. Paroxysmal nocturnal hemoglobinuria on flow cytometry without signs of hemolysis.

Pathophysiology

All cells possess proteins attached to their membranes that are responsible for carrying out a wide range of functions. 

There are several ways to attach proteins to the cell membrane. Paroxysmal nocturnal hemoglobinuria occurs as a result of a defect in one of these mechanisms.

The enzyme phosphatidylinositol glycan (PIGA) is needed to make glycosylphosphatidylinositol (GPI), the molecule that attaches proteins to the cell membrane. 

The gene encoding PIGA is located on the X chromosome which means that only one copy of the PIGA gene is present in each cell (initially, the female has two copies, but one of them remains silent through the inactivation of the X chromosome). 

If a mutation occurs in this gene, there may be a defect in PIGA, which leads to an imbalance in the stability of the GPI index. 

When this transformation occurs in the bone marrow stem cell of the bone marrow (which is used to make red blood cells as well as white blood cells and platelets), all of the resulting cells will be defective as well. 

Many of the GPI-binding proteins on the cell membrane are used to protect the cell from damage by the complement system, and without these fixatives, cells become more targeted by the complement proteins. 

The complement system is part of the immune system and helps destroy invading microorganisms. 

Without proteins that protect them from the complement system, red blood cells would be destroyed. 

The main proteins involved in this task are the wear-accelerating factor (DAF), which disrupts the formation of C3 convertase, and CD59, which binds the membrane-attacking complex and prevents C9 from binding to the cell.

The increased destruction of red blood cells leads to anemia. The increase in the rate of blood clotting is due to a defect in the platelets in the platelets as a result of binding by the complement system, or perhaps due to Low levels of nitrogen monoxide.

The symptoms of esophageal spasm, erectile dysfunction, and abdominal pain are attributed to the fact that hemoglobin has been leaked during the binding of hemolysis to circulating 

nitric oxide and this substance are necessary to relax the involuntary muscles of the voluntary muscles.

This theory is supported by the fact that these symptoms are supported by the administration of nitrates or sildenafil (Viagra), which improve the effect of nitrogen oxide on muscle cells. 

There is a suspicion that chronic hemolysis causes chronic nitrogen oxide depletion which may lead to the development of pulmonary hypertension (increased pressure in the blood 

vessels of the lung), which in turn increases the systolic load on the heart and also causes heart failure.

treatment

long-term

Curative treatment is bone marrow transplantation

Non-curing treatments include immunosuppressant, Eculizumab, which is an anti-C5 antibody (C5) Rosti v. 

The molecular basis of Paroxysmal Nocturnal Ha myoglobinuria 2005 85 82-871, anticoagulants, antibiotics, supportive therapy (blood transfusion, folic acid, iron), and other treatments (corticoids, androgens, and erythropoietin).

references

Paroxysmal nocturnal hemoglobinuria is a chronic condition. For patients with only a small clone and some problems, flow cytometry every six months gives information on the 

severity and likelihood of possible complications. Because of the high risk of thrombosis in PNH patients, prophylactic treatment with warfarin reduces the risk of thrombosis in their patients through a large clone (50 percent of type III white blood cells). 

cite journal author Hall C, Richards S, Hillmen P Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal h hemoglobinuria (PNH) journal Blood volume 

102 issue 10 pages 3587–91 the year 2003 month Nov ber pmid 12893760 doi 10.1182/blood-2003-01 -0009 URL http://bloodjournal.h atologylibrary.org/cgi/content/full/102/10/3587

Thrombolytic episodes are treated as in other patients, but since PNH is a cause of the persistence of this condition 

it is likely that treatment with warfarin or similar drugs should continue long after the thrombotic episode has occurred.

acute heart attacks

There is disagreement as to whether steroids (eg prednisolone) can reduce the severity of hemolytic crises. 

A blood transfusion may be required for treatment, in addition to the importance of correcting anemia, and this prevents the production of PNH cells by the bone marrow, and also prevents hemolysis indirectly. 

With the passage of time, the amount of iron decreases due to its loss in the urine, and it may be treated if it is present. Iron treatment can give result in the process of hemolysis as in most of the PNH-producing cells.

A new monoclonal antibody, eculizumab, protects immune blood cells against destruction by inhibiting the complement system. 

It has been shown to be effective in reducing the need for blood transfusions in patients with hemolysis. cite journal author Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on h 

analysis and transfusion require ents in patients with paroxysmal nocturnal h myoglobinuria journal N. Engl. J. Med. volume 350 issue 6 pages 552–9 the year 2004 pm 14762182 doi 10.1056/NEJMoa031688

examination

Tests are done to detect PNH in all people by screening for aplastic anemia and these tests can be done through myelodysplastic syndromes of the resistant type of anemia.

Epidemics science

Paroxysmal nocturnal hemoglobinuria is rare, with an annual rate of 1-2 cases per million population. 

Most cases develop in people who have previously been diagnosed with aplastic anemia or myelodysplastic syndrome. 

In fact, paroxysmal nocturnal hemoglobinuria develops in MDS and also explains why there appears to be a higher rate of leukemia in people with paroxysmal nocturnal hemoglobinuria, as also in MDS it can sometimes turn into leukemia.

25 of the female cases of paroxysmal nocturnal hemoglobinuria were detected during pregnancy. 

This group has a high rate of thrombosis and the risk of death for both mother and child is significantly increased by approximately (20% and 8%, respectively).

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