(1) A 6-year program of research by the Inflammatory Bowel Disease Study Group at the Royal Free Hospital and School of Medicine, London has demonstrated: 1. That Crohn’s disease is associated with profound damage to the mesenteric vascular blood supply, even in areas where tissue or bowel appear macroscopically normal; 2. That Crohn’s disease is a granulomatous vasculitis; 3. That aphthous ulceration is due to damage to underlying blood vessels; 4. That Crohn’s disease is associated with a hypercoagulable state, and that patients with hemophilia rarely develop Crohn’s disease(13);
(2) As early as 1980, increased fibrinogen, increased platelet count, accelerated platelet aggregation rate and platelet retention rate were found. This hypercoagulability is thought to contribute to the clinical picture of these diseases and may prove useful as an index for determining the severity and prognosis of such cases and for deciding the indication for surgery. Furthermore, in cases where there is a marked increase in coagulability, combined anticoagulant therapy is thought necessary to improve the course of both ulcerative colitis and Crohn’s disease.
(3) In 1983 study was undertaken in view of the higher incidence of thromboembolism in patients with Crohn’s disease. The blood coagulation system was studied in 12 patients previously operated for Crohn’s disease (8 cases of ileitis, 4 cases of colitis) and followed as out-patients. In 75% of cases, the disease was in an inactive stage. Eight patients showed slight lipid malabsorption. Serum levels of fibrinogen, platelets and factor V were shown to be significantly increased (p less than 0.001) as compared to controls. Prothrombin time and factors II, VII and X were shown to be decreased, while factors VIII and IX and antithrombin III were not significantly altered. Thrombocytosis and hyperfibrinogenemia, as reported in literature, seem to determine a condition of blood hypercoagulability, playing therefore a primary pathogenetic role in the genesis of thromboembolism in patients with Crohn’s disease.
(4) The etiology of Crohn’s disease is unknown. Observations suggest that some sort of luminal agent enters the intestinal mucosa and elicits the special inflammatory reaction. Immunological mechanisms seem to be important. A related but so far largely unrecognised reaction is local activation of the external coagulation system that might initiate the formation of thromboses in small arteries in the intestinal wall. Recent studies indicate that microinfarcts due to arterial thromboses at the level of the muscularis propria may be an important pathogenetic mechanism in Crohn’s disease.
(5) Thromboembolism seems to be a significant and serious complication
in Crohn’s disease (CD), and multifocal microvascular infarction of the
intestinal mucosa may be an important effector mechanism in the pathogenesis
of CD.Eighty patients with CD, 47 with inactive (Crohn’s disease activity
index (CDAI) < 150) and 33 with active disease, and 80 healthy controls
were investigated in this study. RESULTS: Fibrinogen was significantly
higher in patients with active CD (median 535 mg/dl; interquartile range
402-620 mg/dl) than in patients with inactive CD (357 mg/dl; 300-467 mg/dl)
or controls (268 mg/dl; 231-299 mg/dl).
An important link between hypercoagulativity, higher levels of fibrinogen
and hypertension( high blood pressure ) was noted in several papers,
and increased fibrinogen condition can be regarded as a strong
and independent predictor of cardiovascular risk.
(6) This study was aimed at investigating haemostasis parameters in patients (pts) with arterial hypertension (AH) before any medical treatment and to correlate these findings with those in healthy normal Greek population. The hypertensive patients had significantly higher levels of fibrinogen (327.75 +/- 51.36 vs. 272.84 +/- 46.8 mg/dl). These preliminary data suggest that in pts with mild to moderate AH, before any medical treatment, there are significantly higher levels of fibrinogen, tPA-Ag and PAI-1 compared with normal volunteers, whereas there are significantly lower a antiplasmin levels. These findings indicate a disturbance in the haemostasis balance with hypercoagulability and fibrinolytic deficiency.
(14) Raised circulating von Willebrand factor is a recognised marker of vascular injury. That serum von Willebrand factor is raised in quiescent as well as active Crohn’s disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder.
(16) Coagulation factor XIII is a plasma transglutaminase involved in crosslinking of fibrin, the last step of the coagulation system and a connective tissue factor contributing to the wound healing process. Factor XIIIA was significantly decreased in Crohn’s disease, the lowest level was observed in patients with intestinal bleeding. Factor XIIIA subunit is an indicator of Crohn’s disease activity. Our study suggests that a low factor XIIIA level is related to the presence of intestinal lesions and might be linked to intestinal repair mechanisms.
(13) Crohn’s disease and ulcerative colitis seem to be rarely associated
with inherited diseases of coagulation. Using a postal and telephone questionnaire
survey sent to directors of all 129 hemophilia centers in the United
Kingdom, the number of patients with inflammatory bowel disease and either
hemophilia or von Willebrand’s disease was determined. RESULTS: Of 6433
patients with hemophilia and 3129 patients with von Willebrand’s disease,
4 cases of Crohn’s disease were reported compared with expected 11.97-16.58
cases (standardized morbidity ratio, 0.33-0.24; 95% confidence interval,
0.90-0.01; P < 0.05). CONCLUSIONS: This epidemiological study provides
further evidence that thrombosis and vascular occlusion may be important
in the pathogenesis of inflammatory bowel disease.
Here are some studies offering treatments for this condition:
(7) It has been suggested that microvascular thrombosis related to vasculitis
and procoagulant factors activation may contribute to the pathogenesis
of Crohn’s disease (CD). Anticoagulant and antiinflammatory properties
of heparin may be useful in the treatment of active inflammatory bowel
diseases. All patients were clinically and biologically evaluated every
week for the 4-weeks treatment period and followed up every 2 weeks for
2 months after the end of heparin treatment. After 4-weeks treatment,
7/13 patients (54 %) fulfill the remission criteria (CDAI < 150) and
3 other patients reported significant clinical improvement ([Delta-bar]
CDAI>100); 3 patients failed to respond. The mean CDAI decreased from
315 (95%CI:260-369) before treatment to 165 (95%CI:107-222) at the end
of heparin treatment (p<0.004). The mean C-reactive protein decreased
from 80.5 mg/l (95%CI:45-115) before treatment to 35 mg/l (95%CI:18-52)
(p<0.007) after 1-week treatment. Among responders, 6 patients were
still in remission 3 months after the end of treatment and 1 patient had
a relapse at week 6. Conclusions: These results suggest that heparin treatment
may be effective in patients with active CD.
CCFA's
page on Heparin
(8) It has been demonstrated that in vivo, nitroglycerin (NTG) increased intraplatelet cGMP concentrations and inhibited platelet function( aggregation ); one mechanisms of this effect is likely to be related to nitric oxide liberation from NTG bioconversion. As an anecdotical account, I have read on the web a question from a Crohn's patient asking if there is a link between Crohn's and heart since he was initially misdiagnosed with a heart attack because the pain responded to nitro.
(9) We examined whether the pathological changes caused by intravascular coagulation could be suppressed by administration of antithrombin III (AT III), an endogenous inhibitor active to thrombin and factor X a. Intravascular coagulation was induced in Wistar rats. The prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all pathological changes in a dose-dependent manner. These findings suggest that intravascular coagulation plays a significant part in the pathophysiology of hypertension of pregnancy and that AT III concentrates may have therapeutic potential in the treatment of this condition.
Beneficial effects of Coagulation Factor XIII supplementation in severe ulcerative colitis have been observed and also in the treatment of Crohn's disease fistulas(15).
(10) The aim of this study was to assess the effects of aerobic exercise on resting and 24-hour blood pressure (BP), left ventricular mass (LVM), plasma fibrinogen and factor VII (FVII). For this purpose 14 sedentary subjects with untreated diastolic BP between 90 and 104 mm Hg completed a 12-week supervised exercise program. Exercise-mediated increase in aerobic fitness was associated with a significant reduction in resting systolic and diastolic BP, mean systolic and diastolic 24-hour BP and LVM index. As for the coagulation parameters only the concentration of fibrinogen significantly decreased whereas FVII remained unchanged. The 8 subjects that resumed a sedentary life-style were reexamined 2 months later: their resting BP, 24-hour BP and fibrinogen concentration returned to baseline values. Our study underlines the usefulness and safety of regular physical exercise in mild hypertension.
(11) An elevated plasma fibrinogen level is increasingly accepted as
an independent risk indicator of cardiovascular disease. This has enhanced
the interest in identifying agents that can normalize elevated plasma fibrinogen
levels. One group of agents with this capacity are the fibric acid derivatives,
e.g. ciprofibrate and gemfibrozil. We studied fibrinogen levels
after 12 weeks of treatment with ciprofibrate (n = 48) and gemfibrozil
(n = 51) in hypercholesterolenic patients. After 12 weeks of treatment,
the fibrinogen levels were significantly decreased (p < 0.0005) with
both drugs, although the decrease in the ciprofibrate group (mean 3.4
g/l pre-treatment to 2.4 g/l after 12 weeks) was larger than in the gemfibrozil
group (mean 3.4 g/l to 3.0 g/l). The lipid lowering effect was comparable
for the two drugs but there was no correlation for either ciprofibrate
or gemfibrozil between the lipid lowering and the magnitude or the velocity
of the fibrinogen lowering effect. This suggests that a new, as yet unknown,
mechanism is involved in fibrinogen lowering by fibrates.
(12) In a placebo-controlled study the effect of ginger and
fenugreek was examined on blood lipids, blood sugar, platelet aggregation,
fibrinogen and fibrinolytic activity. The subjects included in this study
were healthy individuals, patients with coronary artery disease (CAD),
and patients with non-insulin-dependent diabetes mellitus (NIDDM) who either
had CAD or were without CAD. In patients with CAD powdered ginger administered
in a dose of 4 g daily for 3 months did not affect ADP- and epinephrine-induced
platelet aggregation. Also, no change in the fibrinolytic activity and
fibrinogen level was observed. However, a single dose of 10 g powdered
ginger administered to CAD patients produced a significant reduction in
platelet aggregation induced by the two agonists.
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