The monitoring of radiolabeled fibrinogen is a hospital technique which is used in an attempt to detect the early formation of thrombii (clots) in patients so that medical treatment may be initiated. For thrombosis to occur, two conditions are necessary, shock and hemostasis (static blood). In a hospital environment, shock to the system of a patient may be the result of different causes, but most typically results from surgery or myocardial infarction (heart attack). The hemostasis is most prevalent in the lower extremities of patients who are bed ridden and inactive. A thrombus in a patient typically develops in the deep veins of the legs and may break away and be flushed by the blood stream into the lungs resulting in pulmonary embolism. Pulmonary embolism is an extremely serious complication to any patient. A significant percentage of pulmonary embolii in patients result in fatalities.
Fibrinogen is normally present in the system of a patient and it plays a key role in the formation of a thrombus as it is incorporated into the thrombus. Thrombus formation may occur immediately after surgery or may be delayed for many days. Fibrinogen labelled with Iodine-125 is the most convenient way of detecting and following the progress of deep vein thrombosis.
Fibrinogen monitoring has been proven accurate in the detection of deep vein thrombosis between mid-thigh and the calf of a patient's leg. Although the clinical correlation between deep vein thrombosis and pulmonary embolii from the deep veins is still under investigation, there is a strong inference of high risk which may be drawn from the detection of deep vein clot formation. Once detected, preventive treatment may be prescribed, typically the administration of an anti-coagulant drug such as heparin.
There is typically a higher risk of thrombosis to patients who are over 40 years of age, who are overweight, and who smoke. While the danger of thrombosis is most acute to hospital patients who have undergone surgery, it is thought that thrombosis may be a problem in stroke patients, out patients, obstetric-gynecology patients and any patient suffering from hypercoagubility of the blood from one of a number of causes. In fact, the development of thrombosis and resulting pulmonary embolism is considered by some to be the leading cause of unexpected hospital death.
Radiolabeled fibrinogen is considered to be the best pharmaceutical available for use in detecting post surgical deep vein thrombosis since labeled material can be injected pre-operatively. Routine patient monitoring conducted over a 4 or 5 day period post-operatively is thereafter performed. A second injection may be required if further monitoring is indicated. While various labeling substances have been used with fibrinogen, the radioisotopes of iodine are considered to be the best labels or tags. While each of these radioisotopes has its own advantages and disadvantages, Iodine-125 is the most broadly used and seems to be the most satisfactory radioisotope for use in labeling fibrinogen to allow deep vein thrombosis monitoring of patients in prognostic studies. (For diagnostic studies or formed clots other isotopes may be superior). Iodine-125 emits gamma radiation with characteristic energy peaks. A differential discriminator may be used to bracket these peaks and isolate an energy range from about 20 to 100 thousand electron volts both from higher energy and lower energy background.
In a typical fibrinogen monitoring situation, a patient is injected with 100 microcuries of Iodine-125 in one milligram of fibrinogen pre-operatively. While the patient is recovering from surgery, fibrinogen monitoring is conducted. In this procedure, a portable sodium iodide scintillation detector is placed over the heart for a reference reading to normalize to the concentration of I-125 in the blood. The detector is then moved longitudinally down the anterior of the thigh and posterior of the calf of each leg in approximately two inch increments. Readings are recorded on a patient record chart at each increment as percentages of the count obtained over the heart (Precordial Count). The patient is checked and rechecked in this manner at approximately 24 hour intervals, or more frequently if indicated. If the counts at any measuring point along the patient's leg exceeds the reference rate over the heart by more than 20%, or if the counts at any one segment exceed the two adjacent segments or the corresponding point on the other leg by more than 20%, a thrombus is considered to be present.
There are several serious deficiencies in all the instruments presently available for use in fibrinogen monitoring, however. The monitoring process is extremely time consuming because the hospital staff member manipulating the fibrinogen monitor must use one hand to position the patient's leg and hold the scintillation detector probe in position while operating a separate processing and display console and manually recording the readings obtained on a patient record chart with the other hand, or alternatively a second staff member is required to record the readings that the monitoring staff member is acquiring as the acquisition process often requires the use of both hands. In addition, there are many instances where only a small number of radioactive events are detected from the labeled fibrinogen. In this connection, the present instruments provide no safeguard against the measurement and recordation of statistically insignificant data due to an extremely low level of fibrinogen concentration or because of mispositioning of the probe containing the photomultiplier tube and scintillation crystal. Statistical fluctuations are of particular concern where the instrument operator is deriving readings from an analogue meter, as is the case with the instruments presently available.
A further inadequacy of the present instrumentation is the form of display, which produces a representation of the pulse count rate from the scintillation probe only as the position of a needle on a ratemeter scale. The length of time required to ascertain that the needle has stabilized and to visually interpolate a reading from the ratemeter scale unnecessarily lengthens the time required to obtain each reading at each measurement point along the patient's legs.