heparitin-sulfate and Critical-Illness

Topics: Acute Kidney Injury; Anticoagulants; Chondroitin Sulfates; Citrates; Critical Illness; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Humans; Prostaglandins; Renal Replacement Therapy; Sodium Citrate

Systemic inflammatory illnesses (such as sepsis) are marked by degradation of the endothelial glycocalyx, a layer of glycosaminoglycans (including heparan sulfate, chondroitin sulfate, and hyaluronic acid) lining the vascular lumen. We hypothesized that different pathophysiologic insults would produce characteristic patterns of released glycocalyx fragments. We collected plasma from healthy donors as well as from subjects with respiratory failure due to altered mental status (intoxication, ischemic brain injury), indirect lung injury (non-pulmonary sepsis, pancreatitis), or direct lung injury (aspiration, pneumonia). Mass spectrometry was employed to determine the quantity and sulfation patterns of circulating glycosaminoglycans. We found that circulating heparan sulfate fragments were significantly (23-fold) elevated in patients with indirect lung injury, while circulating hyaluronic acid concentrations were elevated (32-fold) in patients with direct lung injury. N-Sulfation and tri-sulfation of heparan disaccharides were significantly increased in patients with indirect lung injury. Chondroitin disaccharide sulfation was suppressed in all groups with respiratory failure. Plasma heparan sulfate concentrations directly correlated with intensive care unit length of stay. Serial plasma measurements performed in select patients revealed that circulating highly sulfated heparan fragments persisted for greater than 3 days after the onset of respiratory failure. Our findings demonstrate that circulating glycosaminoglycans are elevated in patterns characteristic of the etiology of respiratory failure and may serve as diagnostic and/or prognostic biomarkers of critical illness.

Topics: Adult; Aged; Chondroitin Sulfates; Critical Illness; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Lung; Male; Middle Aged; Respiratory Insufficiency

To evaluate the effectiveness and the safety of danaparoid sodium in the treatment of critically ill patients with standard unfractionated heparin-induced thrombocytopenia (HIT) or low-molecular-weight HIT.. University hospital.. Retrospective analysis of 42 consecutive critically ill patients who were admitted for HIT between October 1992 and February 1997 and were treated either with therapeutic or prophylactic doses of danaparoid sodium.. Among the 26 patients treated with therapeutic doses, neither new thrombotic complications nor thrombosis extension was clinically suspected. Two deaths were directly related to lower limb acute arterial thrombosis associated with HIT. Two major hemorrhagic complications were observed when aspirin in addition to danaparoid sodium was administered. When danaparoid sodium was used in prophylactic doses (20 courses of treatment) to prevent either postsurgical or medical thrombotic complications, no thrombotic event was observed. No death related to HIT or danaparoid sodium treatment was observed. One aggravation of a postsurgical cerebral lesion was observed. During danaparoid sodium treatment, a persistence or a recurrence of thrombocytopenia was observed in 6.5% of patients without thrombotic complications.. Danaparoid sodium appears to be an efficient and safe treatment in critically ill patients with HIT. The concomitant use of aspirin in addition to danaparoid sodium seems to represent an important additional hemorrhagic risk that should be avoided in patient management.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation Factors; Chondroitin Sulfates; Critical Illness; Dermatan Sulfate; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Heparitin Sulfate; Humans; Injections, Subcutaneous; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Count; Recurrence; Retrospective Studies; Safety; Thrombocytopenia; Treatment Outcome

Topics: Anticoagulants; COVID-19 Drug Treatment; Critical Illness; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Inflammation; Protein Binding; Pulmonary Gas Exchange; Sepsis

Heparin-induced thrombocytopenia (HIT) is the most common form of drug-induced immune-mediated thrombocytopenia. HIT may be aggravated by life-threatening arterial and venous thrombosis and, to a lesser extent, hemorrhagic complications. We investigated the incidence of thromboembolic and hemorrhagic complications in critically ill patients with the multiple organ dysfunction syndrome and HIT.. Case-control study.. A 33-bed general intensive care unit in a university-affiliated teaching hospital.. Twenty consecutive patients with laboratory-proven HIT compared with 20 contemporary, consecutive patients without HIT.. Unfractionated heparin or low-molecular-weight heparin were replaced by danaparoid sodium in patients with HIT.. Heparin-induced thrombocytopenia was proven by a positive platelet aggregation test. The HIT group consisted of 14 males and 6 females aged 65.2+/-10.8 years (mean +/- standard deviation) with APACHE II scores of 26.7+/-5.4. Thrombocytopenia less than 100 x 10(9)/l developed within 6.4+/-7.0 days. In 12 patients thrombocytopenia resolved after discontinuation of unfractionated heparin in 8.8+/-6.4 days. Arterial and venous thromboembolic complications occurred more frequently in HIT patients than in non-HIT patients (10/20 (50%) versus 0/20 (0%); chi-square p<0.001). Hemorrhagic complications also occurred more frequently in HIT patients than in non-HIT patients (17/20 (85%) versus 7/20 (35%); chi-square p=0.001).. In critically ill patients with HIT, the incidence of thromboembolic complications and hemorrhagic complications was remarkably high.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Chondroitin Sulfates; Critical Illness; Dermatan Sulfate; Drug Combinations; Female; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Risk Factors; Thrombocytopenia; Venous Thrombosis

Heparin binds to platelets and can cause platelet proaggregating and potentiating effects, possibly causing thrombocytopenia, particularly in patients in intensive care with hyperaggregable platelets. In this study we compared the platelet proaggregating and potentiating effects of unfractionated heparin (UH), 2 low molecular weight (LMW) heparins, enoxaparin and dalteparin, and a heparinoid, danaparoid sodium (orgaran), to platelets of an ICU patient population and a normal control group. In both populations UH caused platelet aggregation in a dose-dependent manner. This occurred in the therapeutic range of the drug, with as little as 0.5 U/ml UH. The LMW heparins caused less and the heparinoid least platelet aggregation. Generally, the aggregation observed in ICU patients was greater than in the normal population. The potentiating effects of the 4 drugs in association with physiological agonists was examined. Similar patterns of potentiation were observed in both populations, with UH causing significant enhancement of platelet aggregation, the LMW heparins intermediate and heparinoid least enhancement. There was substantial variability in the individuals' platelets' reactions to the drugs, in particular to UH. Our findings suggest that UH has the greatest effect, the low molecular weight heparins an intermediate effect and the heparinoid the least propensity to cause platelet activation.

Topics: Adenosine Diphosphate; Adult; Aged; Anticoagulants; Chondroitin Sulfates; Critical Illness; Dalteparin; Dermatan Sulfate; Drug Synergism; Enoxaparin; Epinephrine; Female; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Intensive Care Units; Male; Middle Aged; Platelet Aggregation; Reference Values

Topics: Chondroitin Sulfates; Critical Illness; Dermatan Sulfate; Extracorporeal Circulation; Female; Glycosaminoglycans; Hemofiltration; Heparinoids; Heparitin Sulfate; Humans; Male; Middle Aged; Multiple Organ Failure; Renal Dialysis; Thrombocytopenia