Natural degradation or clearance
Unfractionated heparin has a half-life of about one to two hours after infusion, whereas low-molecular-weight heparins half-life is about four times longer. Lower doses of heparin have a much shorter half-life than larger ones. Heparin binding to macrophage cells is internalized and depolymerized by the macrophages. It also rapidly binds to endothelial cells, which precludes the binding to antithrombin that results in anticoagulant action. For higher doses of heparin, endothelial cell binding will be saturated, such that clearance of heparin from the bloodstream by the kidneys will be a slower process. Chemistry
Heparin structure
Native heparin is a polymer with a molecular weight ranging from 3 to 30 kDa, although the average molecular weight of most commercial heparin preparations is in the range of 12 to 15 kDa. Heparin is a member of the glycosaminoglycan family of carbohydrates (which includes the closely related molecule heparan sulfate) and consists of a variably sulfated repeating disaccharide unit. The main disaccharide units that occur in heparin are shown below. The most common disaccharide unit* (see below) is composed of a 2-O-sulfated iduronic acid and 6-O-sulfated, N-sulfated glucosamine, IdoA(2S)-GlcNS(6S). For example, this makes up 85% of heparins from beef lung and about 75% of those from porcine intestinal mucosa.Not shown below are the rare disaccharides containing a 3-O-sulfated glucosamine (GlcNS(3S,6S)) or a free amine group (GlcNH3+). Under physiological conditions, the ester and amide sulfate groups are deprotonated and attract positively charged counterions to form a heparin salt. Heparin is usually administered in this form as an anticoagulant.
Most individuals diagnosed with chancroid have visited countries or areas where the disease is known to occur frequently, although outbreaks have been observed in association with crack cocaine use and prostitution.Chancroid is a risk factor for contracting HIV, due to their ecological association or shared risk of exposure, and biologically facilitated transmission of one infection by the other. Approximately 10% of people with chancroid will have a co-infection with syphilis and/or HIV. Pathogenesis
H. ducreyi enters skin through microabrasions incurred during sexual intercourse. The incubation period of H. ducreyi infection is 10 to 14 days after which there is progression of the disease. A local tissue reaction leads to development of erythomatous papule, which progresses to pustule in 4–7 days. It then undergoes central necrosis to ulcerate. Diagnosis
Variants
Some of clinical variants are as follows. Laboratory findings
From bubo pus or ulcer secretions, H. ducreyi can be identified using special culture media; however, there is a <80% sensitivity. PCR-based identification of the organisms is available, but none in the United States are FDA-cleared. Simple, rapid, sensitive and inexpensive antigen detection methods for H. ducreyi identification are also popular. Serologic detection of H. ducreyi uses outer membrane protein and lipooligosaccharide. Most of the time, the diagnosis is based on presumptive approach using the symptomatology which in this case includes multiple painful genital ulcers.