When it comes to genetics, things can be a little confusing. The internal mechanism is far more complicated than one may suspect. Among all the genetic abnormalities paroxysmal nocturnal hemoglobinuria is rare. In this condition, hemoglobin is excreted in urine after a series of abnormal changes take place in the body, especially red blood cells. The red blood cells have a compliment in their membrane’s composition, which they need for their proper functioning.
A factor called Decay Accelerating factor (DAF) protects the red blood cells from damage mediated by the compliment. DAF is secured by a protein in the body called GPI(Glycosylphosphatidylinositol) that is an anchoring protein. Absence of this protein leads to the absence of DAF, making the cell susceptible to compliment mediated damage.
After these changes take place this is followed by intravascular hemolysis that occurs in episodes mostly at night. Here the mechanism of sleep plays its part.
During sleep, the body goes in slight acidosis that activates the compliment and the damage can occur more easily. This damage caused by the compliment destroys or breakdown the red blood cell, white blood cells, and the platelets. The damage that occurs during night exhibits its effect in the morning by excreting hemoglobin in the urine hence called paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria:
This condition is mostly seen in pregnant women, individuals with liver damage. It is a genetic condition that involves difficult and complex treatment plans that are further discussed according to the condition of the patient. For screening of this disease sucrose test is used. For confirmation of this disease acidified serum test is recommended.
PNH is fatal in most conditions as the intravascular damage that occurred related in thrombus formation that is the blood clot that forms in the vessel and stays there. Thrombosis in the hepatic, portal and cerebral veins can travel to any part of body obstructing the blood flow and causing death.
The complications and risk factor of this disease include iron deficiency anemia due to chronic loss of hemoglobin in urine 9hemoglobinuria) and acute myeloid leukemia AML that occurs in 10% of cases. (Sattar H.A. et., al 2015)
Introduction to hemoglobinuria
It is considered it the symptoms are monitored carefully then one might diagnose the disease early and get treatment sooner than later. Hemoglobinuria when taken a serious sign as it is an abnormal constituent in the urine.
One might suspect that what might be the reason behind its presence in urine. When observed with the naked eye the urine is deep red to brown and gives a positive test for hemoglobin. It must not be confused by hematuria which is the presence of RBCs in urine, as there are no erythrocyte sediments found in this condition.
The test for proteinuria may not be positive unless the concentration of hemoglobin is high enough to raise a red flag.
There is a natural system of the body that disease prevails when it has crossed all of the internal barriers that are within our system. Once all the thresholds are crossed the infection start showing symptoms and its presence like in this case under normal conditions free hemoglobin present in plasma split themselves into dimers that are instantly bound to haptoglobins and engulfed by hepatocytes into bilirubin, amino acids, and iron by the action of macrophages.
If the haptoglobins are saturated that is if their capacity to hold free hemoglobin is exceeded than hemoglobin dimers starts to accumulate in the plasma first causing a condition called hemoglobinemia. Then after the blood reaches the kidney for filtration is reabsorbed and degraded by the proximal tubule cells it is excreted via urine causing hemoglobinuria.
In another condition in the body when hemoglobin that is separated from circulatory erythrocytes is converted to bile pigment of the reticuloendothelial system.
But when the threshold for this normal percentage exceeds its limit to remove hemoglobin, it is accumulated in the blood until the kidneys are unable to filter them out and the renal threshold to filter this floating hemoglobin exceeds this free hemoglobin starts to get excreted through urine as body needs to excrete things that are not needed or may harm the other systems.
The continuous excretion of hemoglobin in the blood causes aplastic anemia and iron deficiency anemia, resulting in constant depletion of iron stores and continuous stress on different body organs including the liver.
Deficiency of Hemoglobin
Prolonged deficiency of hemoglobin in the body and depleting stores means that the red blood cells that are forming have defected and the one that will be produced will have the same defect as well.
When it comes to its treatment the only way to treat is by bone marrow transplant, which deactivates the compliment’s activation using a monoclonal antibody called Eculizumab. The inactivation of compliment stops the process when the compliments get activated during night time and the process terminates at the start.
The question arises what happens after a person has PNH or hemoglobinuria. The answer is after diagnosis the quality of life of the patient starts decreasing gradually as this is a chronic condition that gives the patient time to live.
The treatment options for this condition is limited, with the passage of time more conditions start to develop with it. But it is curable with bone marrow transplant, the option that is not affordable for most of the people in the world.
Research and experiments should be conducted to find a cure for this disease, who knows what more we find. (Wilson D.A et., al 2012)
Sattar, A. A. (2015). Fundamentals of Pathology (second). Chicago, Illinois.Wilson, D. A. (2012). Clinical Veterinary Advisor the Horse