Upshaw–Schulman syndrome (USS) is the recessively inherited form of thrombotic thrombocytopenic purpura (TTP), a rare and complex blood coagulation disease.

The presentation of an acute USS episode is variable but usually associated with thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytes on the peripheral blood smear,[3] fever and signs of ischemic organ damage in the brain, kidney and heart.

[4] Patients may also report signs and symptoms as a result of (microangiopathic) hemolytic anemia, such as (dark) beer-brown urine, (mild) jaundice, fatigue and pallor.

Cerebral symptoms of various degree are present in many patients, including headache, paresis, speech disorder, visual problems, seizures and disturbance of consciousness up to coma.

Severe manifestations of heart or lung involvements are rare, although affections are not seldom measurable (such as ECG changes).

[6][7] The ADAMTS protease family contains enzymes that process collagen, cleave inter-cellular matrix, inhibit angiogenesis and blood coagulation.

Increased vWF levels in the circulation are leading to a higher demand of ADAMTS13, which is lacking in USS, and can bring forward a TTP episode.

[8] In its uncut form, (ultra large) vWF's heightened stickiness and interlinking causes spontaneous platelet binding and blood clotting.

[3] vWF in the normal length loses its heightened stickiness and spontaneous crosslinking activity to only form blood clots when needed.

[3] A diagnosis of TTP is based on the clinical symptoms with the concomitant presence of thrombocytopenia (platelet count below 100×109/L) and microangiopathic hemolytic anemia with schistocytes on the blood smear, a negative direct antiglobulin test (Coombs test), elevated levels of hemolysis markers (such as total bilirubin, LDH, free hemoglobin, and an unmeasurable haptoglobin), after exclusion of any other apparent cause.

[2] If a severe ADAMTS13 deficiency is present an ADAMTS13 inhibitor assay is needed to distinguish between the acquired, autoantibody-mediated and the congenital form of TTP (USS).

[1][9] The intensive plasma-therapy is generally stopped when platelet count increases to normal levels and is stable over several days.

[1][2] Not all affected patients seem to need a regular preventive plasma infusion therapy, especially as some reach long-term remission without it.

[24] Regular plasma infusions are necessary in patients with frequent relapses and in general situations with increased risk to develop an acute episode (as seen above) such as pregnancy.

Another drug in development is targeting vWF and its binding sites, thereby reducing vWF-platelet interaction, especially on ULVWF during a TTP episode.