Upshaw-Schulman Syndrome

By | June 10, 2022

Upshaw-Schulman syndrome (USS) is the hereditary form of thrombotic thrombocytopenic purpura (TTP). The disease is accompanied by microthrombosis in the small blood vessels (capillaries).

What is Upshaw-Schulman Syndrome?

Upshaw-Schulman syndrome is an inherited disorder that affects the blood clotting system. In 1947 the first case of TTP became known. As early as 1966, the physician Schulman described the first USS case. The doctor Upshaw supplemented these records in 1978, so that the disease was known as Upshaw-Schulman syndrome from 1979. For klatskin tumor explained, please visit

Every year 1.7 to 4.5 people out of a million suffer from this form of thrombocytopenic purpura. A synonym for Upshaw-Schulman syndrome is congenital TTP. The symptoms of the disease are very variable. In many cases, hemolytic anemia occurs. Many USS patients require plasma infusions at regular intervals. The disease cannot be cured.


Upshaw-Schulman syndrome is inherited in an autosomal recessive manner. The ADAMTS13 protease is affected by the genetic mutation. This is located on chromosome 9q34. It consists of 1427 amino acids that form different functional areas. Any of these domains can be affected by the mutation in the USS. As a result, the secretion of the ADAMTS13 protease is disturbed or its activity reduced. The main task of this protease is to cleave the multimers of the von Willebrand factor (vWF).

Von Willebrand factor is a glycoprotein that plays an important role in hemostasis and blood clotting. To prevent thrombus formation, the multimers of this factor must be split in good time. In most USS patients, the ADAMTS13 protease activity is usually only 10 percent. Under normal circumstances, this activity is sufficient to cleave the vWF multimers.

An acute episode of thrombotic thrombocytopenic purpura is therefore usually triggered by environmental factors. Triggers are pregnancy, increased alcohol consumption, medication and infections. Here, increased von Willebrand factor is released from the body’s stores. The level in the blood increases and the restricted ADAMTS13 protease is no longer able to cleave sufficient multimers. This leads to a spontaneous coagulation of the blood in the capillaries.

Symptoms, Ailments & Signs

The symptoms of TTP vary greatly. Blood platelets (thrombocytes) are lost as a result of the formation of microthrombi. Most symptoms are caused by a lack of platelets (thrombocytopenia). 90 percent of patients have purpura. The term purpura describes small capillary hemorrhages in the skin, the mucous membranes or in the subcutis. The bleeding is usually spot-like (petechiae).

If the bleeding occurs over a small area, it is referred to as an ecchymosis. Patients often notice hematomas as the first symptom. Even minor impact injuries quickly result in larger bruises. The thrombi in the capillaries are obstacles for the red blood cells (erythrocytes). When trying to pass through the bottlenecks in the small blood vessels, the erythrocytes are often destroyed mechanically.

The result is hemolytic anemia. Destroyed red blood cells are broken down in the spleen. Yellow bilirubin is then produced from the red blood pigment hemoglobin. Bilirubin is normally broken down in the liver and excreted in the urine. In hemolytic anemia, there is so much bilirubin that the liver is unable to break it down. The bilirubin gets into the skin and causes a yellow discoloration there. This is also known as jaundice.

If too much unprocessed bilirubin gets into the urine, it turns it dark orange. Many patients also complain of tiredness and neurological symptoms such as headaches, movement disorders or speech disorders. If microthrombi form in the area of ​​the brain, they can trigger a stroke there. In rare cases, the heart or lungs are also severely affected.

Diagnosis & course of disease

An initial suspected diagnosis can be made based on the symptoms. The laboratory then shows thrombocytopenia and microangiopathic hemolytic anemia. Schistocytes are found in the blood smear. Hemolysis markers such as bilirubin, free hemoglobin, haptoglobin, and LDH are elevated. The Coombs test, a direct antiglobulin test] is negative.

The distinction from similar diseases such as autoimmune hemolytic anemia, Evans syndrome, HELLP syndrome, preeclampsia, eclampsia, cancer or antiphospholipid antibody syndrome is particularly important when making the diagnosis.


Those affected with Upshaw-Schulman syndrome primarily suffer from a high deficiency of platelets. This leads to increased bleeding under the skin, which can usually have a negative effect on the aesthetics of the person concerned. An increased tendency to bleed can also occur, so that even minor injuries or cuts can lead to very heavy bleeding.

Even minor impact injuries can cause severe bruising on the skin from Upshaw-Schulman syndrome. Due to the restricted aesthetics, many of those affected also suffer from inferiority complexes or a significantly reduced sense of self-esteem. Those affected often suffer from headaches or severe movement disorders.

Speech disorders can also occur. Especially in children, Upshaw-Schulman syndrome can lead to delayed or severely restricted development. In severe cases, this can also promote a stroke, which in the worst case can result in the death of the person concerned.

Treatment of the syndrome is carried out with the help of drugs and various therapies. Complete healing is usually not achieved. The life expectancy of the patient is also limited in most cases by the syndrome.

When should you go to the doctor?

The first doctor’s visit for Upshaw-Schulman syndrome is often because of increasing hematoma or capillary bleeding under the skin. Symptomatic similarities to thrombotic thrombocytopenic purpura can be observed in the rarely occurring blood clotting disease.

Those affected experience thrombotic microangiopathy, which leads to vascular occlusions in smaller blood vessels. This leads to insufficient blood flow to the surrounding tissue. The resulting tissue damage can also lead to a doctor’s visit. The symptom situation is very different in those who are acutely affected.

It can be accompanied by fever, non-specific symptoms such as headaches or anemia. Damage to vital organs such as the heart, brain or kidneys caused by ischemia also makes a doctor’s visit necessary. The rare and sometimes late occurrence of this disease is problematic for the doctor.

It requires a specialist who is familiar with hematology. Upshaw-Schulman syndrome can be inherited in an autosomal recessive manner. The syndrome can be detected in newborns as well as in old age. What is striking is the variety of partly non-specific symptoms and their intermittent occurrence.

Nowadays, an early visit to the doctor can ensure that the consequences of the disease can be mitigated. To a certain extent, prophylactic therapy is possible if the disease has already been diagnosed in one of the parents and has therefore been inherited. Whether or not there is recurrence in treated patients with Upshaw-Schulman syndrome varies.

Treatment & Therapy

An acute episode of TTP requires immediate treatment. In the case of mild to moderate courses, the ADAMTS13 protease is replaced in daily plasma infusions. In severe cases, plasma exchange therapy (PEX) is used. Here, the patient’s plasma is almost completely replaced by a donor plasma.

In both cases, platelet-poor fresh-frozen plasma (FFP) is used. However, other plasma products can also be used with ADAMTS13. In contrast to normal plasma infusions, PEX therapy removes all excess multimers of von Willebrand factor. Occasionally there may be side effects.

How many plasma infusions are needed depends on the severity of the disease. As a rule, however, treatment for Upshaw-Schulman syndrome can be ended after a week. Within this time, the platelet count has usually normalized and stabilized. However, other drugs are currently being researched. These are intended to inhibit excessive coagulation during the TTP episode and make plasma infusions superfluous.


Upshaw-Schulman syndrome is an inherited condition. So there is no prevention. The TTP episodes, on the other hand, can be prevented with regular plasma infusions. For prevention, such infusions are usually required every two to three weeks. However, the frequency can also be individually adapted to the patient. In the case of mild courses, preventive plasma infusions should only be carried out in risky situations.


Follow-up care for Upshaw-Schulman syndrome always takes place with regard to the symptoms. Since the disease can take very different courses, the measures must be determined individually. Part of the aftercare is the clarification of the typical neurological symptoms. These include speech and movement disorders or headaches.

After an attack, medical follow-up care is necessary, especially if the heart or lungs are severely impaired. Comprehensive follow-up care is also indicated for changes in the organ systems that are detected during routine checks. This usually includes a physical examination and a patient interview.

The physical examination serves to determine possible changes, urine and blood samples are taken and, if necessary, neurological examinations are also carried out. The most important measure, however, is the planning of further plasma infusions, insofar as these are necessary for the patient. In the case of severe disease progression, the plasma infusion must be repeated every two to three weeks.

As part of the aftercare, any side effects and interactions are discussed and further appointments are made. Follow-up care for Upshaw-Schulman syndrome is carried out by the general practitioner and various specialists such as internists, neurologists and specialists in human genetics. In severe cases, a therapist may also be involved in the treatment.

You can do that yourself

Upshaw-Schulman syndrome requires medical attention. The self-help measures are limited to consulting a doctor at an early stage and having the symptoms clarified. Self-treatment of the typical symptoms is only necessary for a short time, since USS can be treated well with the infusion of blood plasma.

If you are tired, feel unwell or have muscle and joint pain, you should get enough sleep. In the case of fever and pallor, rest also helps to alleviate the symptoms until treatment is initiated. If signs of impaired blood clotting occur, the doctor must be informed. If you experience dizziness, clouded consciousness or speech and movement disorders, you may have a venous occlusion. The patient must go to a hospital immediately before a stroke occurs.

Pain therapy can be supported by various natural remedies in consultation with the doctor. It is best for patients to contact a herbal medicine practitioner for appropriate remedies to relieve the pain and other symptoms of Upshaw-Schulman syndrome. In addition, the doctor must be informed about the course of the disease and unusual symptoms, since there is a high risk of complications with USS.

Upshaw-Schulman Syndrome