The Genetics and Functional Basis of Inherited Platelet, White Blood Cell, Red Blood Cell, and Blood Clotting Disorders.

Blood contains red blood cells, white blood cells, and platelets, as well as a fluid portion termed plasma. We primarily study blood platelets, but sometimes we also analyze the blood of patients with red blood cell disorders (such as sickle cell disease), white blood cell disorders, and disorders of the blood clotting factors found in plasma.

Blood platelets are small cell fragments that help people stop bleeding after blood vessels are damaged. Some individuals have abnormalities in their blood platelets that result in them not functioning properly. One such disorder is Glanzmann thrombasthenia. Most such patients have a bleeding disorder characterized by nosebleeds, gum bleeding, easy bruising (black and blue marks), heavy menstrual periods in women, and excessive bleeding after surgery or trauma. Our laboratory performs advanced tests of platelet function and platelet biochemistry. If we find evidence that a genetic disorder may be responsible, we analyze the genetic material (DNA and RNA) from the volunteer, and when possible, close family members to identify the precise defect.

After volunteers and family members agree to participate, they are seen in the Outpatient Research Center by the Principal Investigator or another physician. A detailed history is obtained, a physical examination is performed, and blood is obtained for further tests. Occasionally patients and family members are requested to return for additional tests. If an abnormality is identified with tests conducted in our research laboratory, we advise the volunteer to have the studies repeated in a laboratory certified to conduct tests on patients.

For normal volunteers, we recruit from laboratory personnel and other volunteers from the NYC area. Patients with sickle cell disease and cardiovascular disease associated with increased intravascular shear forces are recruited from physicians in the New York area who care for such patients. Patients with platelet disorders, coagulation disorders, or white blood cell disorders, are recruited from among patients referred by other physicians to the P.I. for assessment or via the internet.

• Normal
  Normal, healthy volunteers 18 years of age or older of either sex and any ethnic background
• Glanzmann thrombasthenia
  Patients with Glanzmann thrombasthenia or their relatives, end stage renal disease, sickle cell disease or related disorders, inherited qualitative and/or quantitative platelet disorders, inherited disorders of white blood cells, inherited disorders of coagulation

Normal Volunteers Inclusion criteria: Normal, healthy volunteers 18 years of age or older of either sex and any ethnic background.

Exclusion criteria: 1. For studies of platelets that may be affected by antiplatelet therapy, ingestion of aspirin or similar medication in the past week. 2. Having given blood in the last 8 weeks such that the current donation would exceed a total of 250 ml for the 8 week period. 3. Having given blood in the past week such that this donation would result in more than 2 donations in one week.

B. Patients with Glanzmann thrombasthenia or their relatives, end stage renal disease, sickle cell disease or related disorders, inherited qualitative and/or quantitative platelet disorders, inherited disorders of white blood cells, inherited disorders of coagulation (including von Willebrand disease), and patients with diseases associated with increased intravascular shear forces (e.g., obstructive coronary disease, aortic stenosis, and coarctation of the aorta).

Inclusion criteria: Adults and children of either sex and any ethnic background.

Exclusion criteria: 1. For studies of platelets that may be affected by antiplatelet therapy, ingestion of aspirin or similar medication in the past week. 2. If the patient is known to have a hematocrit ≥25 (assay performed in past 3 months), the same blood drawing criteria as in A, with the addition that for children less than 18 years of age, the maximum amount of blood allowed to be donated in an 8 week period is the lesser of 50 ml or 3 ml/kg. 3. If the patient has a hematocrit <25 or if the hematocrit is unknown, the blood drawing limit is the lesser of 20 ml or 1 ml/kg in any 8 week period.