Last week we began studying the history of DVT. The most important advances in the field of DVT therapy occurred during the first half of the 20th century. However, numerous other therapeutic options, sometimes surprising, were tried during this period and later abandoned because of insufficient efficacy.
Even though the mechanisms of venous thrombosis (blood clots) had been discovered by the middle of the 19thcentury, it was closer to the 1920s that a consensus appeared regarding the three factors contributing to thrombosis: stasis, vessel wall alteration, and hypercoagulability (abnormality of blood coagulation that increases the risk of blood clots in the blood vessels).
During the late 19th century and early 20th century, there were a number of breakthroughs that have changed DVT treatment. Many of these were discovered by accident.
1884 – Hirudin first isolated anticoagulant. It was extracted from the saliva of leaches. Could not be used as a powerful anticoagulant until production by genetic engineering in 1986.
1916 – Heparin first anticoagulant that could be effectively used for the treatment of DVT. A medical student, who was doing research to find products which would promote coagulation of blood, noticed some extracts became anticoagulant after prolonged exposure to air. Four years late he discovered true heparin.
1933 – Pure crystalline heparin was produced allowing its use in humans in 1935. The use of heparin became widespread (when available) because of its efficacy. It was administered for 7-10 days and cut the mortality from Pulmonary Embolism among inpatients with symptomatic DVT from 18% to 0.4%.
1941 – Vitamine K antagonists (VKAs) allowed anticoagulant therapy to be extended. Vitamine K is required for the correct production of certain proteins necessary in the blood clotting process. They are structurally similar to vitamin K and act as competitive inhibitors. The action of this class of anticoagulants may be reversed by administering vitamin K until there is no more VKA in the body. Vitamin K antagonists include coumarins which include, but are not limited to warfarin, coumatetralyl, phenprocoumon, acenocoumarol, dicoumarol, and non-coumarin VKAs such as fluindione and phenindione. All can be reversed by administering vitamin K.
1950 – Heparin was still the choice treatment for DVT, but surgical procedures were used for severe cases of DVT. The surgical procedures did not provide substantial clinical improvement.
1958 – First intraluminal “harpgrip” filter showed promise in preventing Pulmonary Embolisms. The filter could block movement of blood clot without significantly affecting the venous system; however it required major surgery and anesthesia for placement.
1967-1970 – The problem of a filter requiring major surgery and anesthesia for insertion was solved with the Mobin–Uddin umbrella. It could be inserted with a simple catheter under local anesthesia. Besides the potential for migration, this filter could cause gradual obstruction of the inferior vena cava. This was partially prevented by coating the filter with heparin.
1981 – Greenfield developed the first true percutaneous filter, which did not necessitate any surgical opening of a vein. However, truly retrievable filters (without a catheter and without persisting venous access) became available for clinical use only two decades ago. Therapeutic trials are currently underway.
1970 – Venography (developed in 1923) became standardized and widely used for confirmation of DVT; physicians no longer treat clinically suspected DVT. This enabled physicians to diagnose and treat DVT while clinically asymptomatic and simplified DVT treatment with anticoagulants, ended bed-rest as a treatment, and allowed home treatment.
1980 – Development of low-molecular-weight heparin (LMWH) was the most significant step in the simplification of anticoagulant therapy. In most cases, it does not require monitoring. Was introduced in Europe and in 10 years was widely used.
1996 – Was demonstrated that LMWH given at home was safe and effective as unfractionated heparin administered in the hospital.
1996 – Evidence that early ambulation with compression stockings lessened pain and counteracted swelling without an increased risk of Pulmonary Embolism. This became widespread treatment and is now recommended treatment.
1997 – The usefulness of compression bandages in preventing post-Thrombotic Syndrome (long-term complications of DVT) shown. Even though Hippocrates prescribed compression bandages to treat leg ulcers, it was not until the late 19th century, after observing that superficial vein clots disappeared rapidly after application of compression bandages, physicians started prescribing compression bandages to their patients with DVT. Compression bandages started to be more widely used when anticoagulants became available. They were usually prescribed at the end of heparin treatment, once ambulation was authorized.
1938 – First Thrombectomy (blood clot removal). Twenty years later this procedure was improved and anticoagulant was added to prevent more blood clots from forming. Surgical thrombectomy is not recommended for routine treatment today. Early blood clot removal has been achieved using pharmacological thrombic agents. (Anticoagulation therapy for some patients is not a choice because of bleeding problems.)
1953 – Plasmin (also produced in the body) used to treat acute blood clots (including isolated DVTs) by dissolving them through intravascular infusion. In the same year streptokinase was also used for the same purpose. Streptokinase causes extra production of plasmin in the body.
It will be many years before the appropriate indications and contraindications are carefully defined about the use of thrombolytic agents, and the optimal approach (catheter directed vs. systemic administration) of the use of these agents to blood clots is identified, allowing the selection of the population at highest risk of Post Thrombotic Syndrome and lowest risk of bleeding. Nevertheless, it is likely that the long-term results, despite being promising, will not dramatically modify the routine management of DVT.
I hope you keep wearing your support socks and support stockings so you are less likely to have to deal with a DVT and DVT treatment!