Nasal toxicity of cocaine: a hypercoagulable effect?

Nasal insufflation of cocaine injures the nasal mucosa and can perforate the septum. Cocaine-induced vasoconstriction resulting in ischemia is one of the methods that may be responsible for this damage. We are determining whether cocaine also produces a hypercoagulable state that may compound factors which have been previously established to cause damage to the nasal mucosa and septum. This study uses Modified Recalcification Time (MRT), a test developed in our laboratory that has the ability to measure the overall coagulation process. Our study revealed no connection between cocaine and enhanced platelet function or monocyte-released tissue factor. The coagulation process was unaffected by the addition of the drug, so we conclude that cocaine does not cause a hypercoagulable state and cannot assist in the explanation regarding the ischemic changes of the nasal septum.

Determination of hypercoagulable state in acute bronchospasm.

The issue of hypercoagulability in acute asthmatic attacks is controversial. This may be due to lack of an appropriate test to monitor overall coagulation. Current hematologic tests do not account for the cellular fraction of blood that has procoagulant activity. Our study uses a clotting assay called the modified recalcification time test that is performed with whole blood to ensure the contribution of all chemical and cellular mediators in the coagulation process, particularly tissue factor. Venous blood samples were obtained from 12 adult patients with acute exacerbation of asthma or chronic obstructive pulmonary disease and compared with samples from 12 age-matched healthy control subjects. By use of the modified recalcification time, the presence of a relative hypercoagulable state was demonstrated in patients with acute bronchospasm. Furthermore, there is an identifiable difference in modified recalcification time value between the patients with acute attacks who required hospital admission versus those discharged from the emergency department.

Effect of methylprednisolone on coagulation.

This in vitro study examined the effects of methylprednisolone on coagulation status. Venous blood samples were collected from 12 adult subjects including healthy volunteers and patients presenting to the emergency department and analyzed for coagulation changes using the modified recalcification time (MRT) test prior to and after the addition of methylprednisolone. Mean +/- SD MRT control values before the addition of methylprednisolone (MRTC) and after (MRTCP) were 5.4 +/- 1.5 and 5.7 +/- 1.3 minutes, respectively. The MRT saline values prior to treatment with methylprednisolone (MRTS) and after (MRTSP) were 5.6 +/- 1.2 and 5.4 +/- 1.1 minutes, respectively. The MRT endotoxin prior to the introduction of steroid (MRTE) and after its addition (MRTEP) were 3.8 +/- 0.8 and 5.2 +/- 1.4 minutes, respectively. The MRTE values in the presence of methylprednisolone were significantly different between groups. This may suggest that the monocyte-stimulated release of the procoagulant tissue factor is inhibited by the corticosteroid, causing the blood to be relatively hypocoagulable.

Complete cartilaginous duplication of the rib cage found in a cadaver: a first reported case.

We discovered a unique case of complete cartilaginous duplication of the rib cage in a cadaver, never previously described in the literature. A retrospective review of the patient's medical records revealed an antecedent history of progressive tobacco-related emphysema leading to death from end stage respiratory failure. Prior imaging studies consisting of plain radiographs and computed tomograms of the chest had failed to show several underlying cartilaginous duplications of the rib cage. The clinical significance and the potential contribution of this entity to this patient's clinical course remains unanswered.

Deceptive prothrombin and activated partial thromboplastin times in alcoholic cirrhosis.

It is believed that perioperative hemorrhage, in the hepatoportal area, results from a coagulopathy. This study determined if this could be quantitated by a modified recalcification time (MRT) test developed in our laboratory. Unlike prothrombin (PT) and activated partial thromboplastin times (APTT), the MRT is performed with whole blood to ensure the role of blood cells and chemicals (particularly tissue factor, a potent procoagulant) in the coagulation process. Candidates for liver transplantation (n = 11) were studied. Samples (5 mL) of citrated venous blood were obtained from the patients. Aliquots (1 mL) from these samples were divided into groups of vials labeled C, S, and E. Groups C and S received 20 microL saline and group E, 20 microL of saline containing 10 micrograms of Escherichia coli endotoxin (055: B5W). Vial C was incubated for 10 minutes and vials S and E for 120 minutes, all at 37 degrees C. Then, the MRT was determined on 300 microL of blood from each vial after adding 40 microL of 0.1M calcium chloride. Mean MRT values (minutes +/- standard deviation) for C (MRTC), for S (MRTS), and for E (MRTE) were compared with like values from healthy controls (n = 29). Despite prolonged PT and APTT values, MRT values were shortened in patients with cirrhosis. This hypercoagulability detected by the MRT exonerates a hemorrhagic coagulopathy and possibly implicates widened and thinned gaps in the walls of the portal venous tributaries as the cause of perioperative hemorrhage.

Role of platelet age in assessment of coagulation.

There are two important reasons why most platelet function studies can be inaccurate. First, platelet function deteriorates when blood is taken out of the vascular tree. Second, tests performed on platelets removed from the blood do not incorporate the role of other cellular and chemical components that may alter platelet activity. This article demonstrates that a coagulation test developed in our laboratory can accurately assess the role of platelet age on the speed of the coagulation of blood. Samples (5.0 mL) of citrated venous blood from 15 volunteers were divided into two groups. One group (n = 6), comprised of subgroups A, B, C, and D of 950 microL aliquots each, was tested within 3 hours. The second group (n = 9), comprised of subgroups E, F, G, and H of 950 microL aliquots each, was tested at 24 hours. The aliquots were added to 50 microL saline without collagen (subgroups A and E), 50 microL saline with 10 micrograms collagen (subgroups B and F), 50 microL saline with 50 micrograms collagen (subgroups C and G), and 50 microL saline with 100 micrograms collagen (subgroups D and H). All collagen-incubated fresh blood samples were significantly more hypercoagulable (shorter recalcification times) compared with the control (no collagen) blood. In the 24-hour-old blood, changes were significant only in the sample with 50 micrograms/mL collagen. We conclude that these data authenticate the role of platelet age in the assessment of the coagulation process.

Modified recalcification time (MRT): a sensitive cancer test? Review of the evidence.

In the past, hypercoagulability causing cancer-related thrombosis (Trousseau phenomenon) remained unproven for lack of an appropriate coagulation test. This review proves that a modified recalcification time (MRT) test can detect cancer-related hypercoagulability. The hallmark of this test involves incorporating tissue factor (TF) in accurately assessing coagulability. Blood from controls and cancer patients was incubated with saline and endotoxin (to enhance clotting ability by monocyte-generated TF). The MRT with saline incubation (MRTS) and the MRT with endotoxin incubation (MRTE) were determined instrumentally. The MRTE is a more inclusive measure of total TF activity than the MRTS in nonadvanced cancer. The MRTE values (minutes +/- standard deviation) were: controls-5.69 +/- 0.8; miscellaneous cancers-3.17 +/- 1.1; head, neck, and colon cancers-3.9 +/- 0.6; breast cancers-3.6 +/- 0.6; gynecological cancers-4.1 +/- 0.9; and prostate cancers-3.4 +/- 1.1. The MRTE, by demonstrating hypercoagulability in nonadvanced (including occult) cancer, qualifies as a more sensitive marker for cancer than the Trousseau phenomenon. The data suggest that this test may be the most sensitive blood test to detect early cancer.

Tumor necrosis factor-induced necrosis: a monocyte-mediated hypercoagulable effect.

The mechanisms by which tumor necrosis factor (TNF) exerts its necrotic effects are somewhat obscure. We hypothesize that TNF, by monocyte activation, produces the procoagulant tissue factor, thus leading to a state of hypercoagulability with resultant thrombotic vascular occlusion and tissue necrosis. To test this hypothesis, modified recalcification time values (in minutes +/- standard deviation) were obtained on aliquots of blood with A) 20 microL of albumin, B) 20 microL of saline containing endotoxin, and C) 20 microL of albumin with 450 units of TNF. No differences were noted if the samples were not incubated. We conclude that TNF, can cause tumor (tissue) necrosis, and since incubation is required, TNF alone (without monocyte activation) has no procoagulant activity.

Are hypertensives hypercoagulable?

Angiotensin II is a prothrombotic vasoconstrictor. This study proves that many hypertensives are hypercoagulable and at risk for myocardial infarction. The modified recalcification time (MRT) test, used to assess hypercoagulability, incorporates the role of tissue factor in coagulation by activating the monocyte with endotoxin to release latent tissue factor. Aliquots of citrated blood obtained from hypertensives and normotensive controls were placed in two groups of vials, one with saline (group S) and one with endotoxin (group E). All vials were incubated at 37 degrees C for 2 hours, citrate neutralized with calcium chloride, and the MRT (in minutes) for group S (MRT S) and for group E (MRT E) was determined. Mean MRT S values +/- standard deviation (SD) for hypertensives (n = 25) and for controls (n = 27) were 6.4 +/- 1.2 and 6.8 +/- 1.2, respectively. The MRT E values were 4.3 +/- 1.2 and 5.7 +/- 0.9 for the hypertensives and controls, respectively. The MRT E, not the MRT S, was significant. Hypertensives had MRT E values < 4.5 minutes, and by our established criteria, were hypercoagulable. We conclude that because hypercoagulability is a risk factor for thrombosis, hypertensives with short MRT E values may be at increased risk for myocardial or other thrombotic events.

Hypertension-related coronary thrombosis: prothrombic role of angiotensin II.

Although hypertension is a major risk factor in acute myocardial infarction, concomitant hypercoagulability causing thrombosis leading to myocardial infarction remains unproven for lack of an appropriate coagulation test. This study was devised to determine whether a modified recalcification time (MRT) test can demonstrate that angiotensin II, a potent vasoconstrictor, also accelerates coagulation to promote thrombosis. The MRT incorporates blood cells and chemical coagulants for maximizing sensitivity. Four groups (A, B, C, and D) of aliquots of citrated human blood were incubated for 2 hours at 37 degrees C after adding to A--20 microL saline, to B--10 micrograms Escherichia coli endotoxin, to C--20 micrograms angiotensin II, and to D--a combination of E coli endotoxin and angiotensin II. The experiment was repeated with nonincubated aliquots. Modified recalcification time values +/- standard deviation in minutes were: A--5.5 +/- 1.5, B--4.6 +/- 1.1, C--4.9 +/- 1.0, and D--3.9 +/- 1.0. Significance (Student's t test) was as follows: B versus A P < .001; C versus A, P < .05; C versus D, P < .001; B versus C, P < .05; and B versus D, P < .001. No significant changes occurred in nonincubated blood. We conclude that angiotensin II has a hypercoagulable effect, as does endotoxin. The hypercoagulability in concert with vasospasm can explain the role of hypertension in acute myocardial infarction. This in vitro study excludes the role of other in vivo mechanisms in the development of angiotensin II-induced hypercoagulability.