Coagulation Disorders

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) are often not optimally diagnosed by many physicians. These are serious but preventable medical conditions. Deep Vein Thrombosis (DVT) is a medical condition which occurs when a blood clot forms in deep vein. These clots usually could develop in the lower leg, thigh, or pelvis. These can also occur in arm. One should have knowledge about DVT, because it can happen to anybody and can cause serious illness, disability and morbidity. DVT is preventable and treatable if detected early.

Pulmonary Embolism (PE) is also referred to as complication of DVT. It happens when part of the clot breaks off and travels through the blood stream to the lungs, causing a blockage called Pulmonary Embolism (PE). If the clot is small; with appropriate treatment, people can recover from PE. However, there could be some damage to the lungs. If the clot is large, it could stop the blood reaching lungs and can be fatal.

Risk Factors that could cause DVT

Anybody can have a DVT. However, the factors listed below could increase the chance if having DVT. The chance increases for someone who has more than one of these factors at the same time.

·         Hospitalization and some major surgery.

·         Being bedridden for long time due to illness.

·         Travelling for extended time beyond four hours in continuity.

·         Older age.

·         Overweight or obese

·         Family history of Venous Thromboembolism (VTE.)

·         During and just after pregnancy.

·         Hormonal contraceptive medication (Estrogen based medication).

·         Hormonal Replacement Therapy (HRT).

·         Trauma due to injury.

Preventing tips for DVT

Following tips could help prevent DVT:

·         Move around as soon as possible after having confined to the bed, after illness, injury, or surgery.

·         If you are at risk of DVT talk to your Physician/Surgeon for appropriate medication.

·         When sitting for long periods of time such as travelling for more than 4 hours; get up and walk around after 1 to 2 hours.

·         Raising and lowering your heels while keeping your toes on floor.

·         Raising and lowering your toes while keeping your heels on the floor.

Symptoms of DVT

Most of the people with DVT have no symptoms at all. The following are the most common symptoms of DVT that could occur in affected part of the body:

·         Swelling

·         Pain

·         Redness of the skin

·         Tenderness

If you have any doubt of having DVT consult your doctor as soon as possible.

Pulmonary Embolism (PE)

One can have Pulmonary Embolism (PE) without any symptoms of a DVT. Signs and symptoms of PE could be:

·         Difficulty in breathing

·         Faster than normal or irregular heartbeat.

·         Uneasiness

Coagulation Mechanisms of our Body

Our blood is a very complex tissue of our body, in the form of a fluid. It plays a variety of roles for homoeostasis. Our blood has cellular and noncellular components uniformly suspended in liquid phase. Blood plays multiple roles in our body for sustain life and longevity. There are three types of cells in our blood:

·         Red Blood Cells (RBCs) or Erythrocytes

·         White Blood Cells (WBCs) or Leucocytes

·         Platelets

Red Blood Cells (RBCs) or Erythrocytes provide red color to our blood. RBCs carry oxygen from lungs to various organs and parts of our body. White Blood Cells (WBCs) provide us natural and acquired immunity. Platelets along with other soluble coagulation factors (CFs) take part in coagulation of blood to safeguard us from internal of external bleeding. There are ‘XIII’ coagulation factors (CFs) in our blood. We know the chemistry and role of all the coagulation factors. Coagulation of Blood occurs through two mechanisms:

·         Intrinsic Pathway and

·         Extrinsic Pathway

Both the coagulation mechanisms involve various coagulation factors and finally lead to activation of factor ‘X’. Factor ‘X’ along with certain factors leads to formation of Thrombin from Prothrombin. Thrombin is central in clotting process, and it converts Fibrinogen to Fibrin; activates factor ‘V’, ‘VIII’ and ‘XI’, leading to generation of more Thrombin and stimulation of Platelets. Further by activating factor ‘XIII’, thrombin favors the formation of cross-linked bonds among Fibrin molecules, thus stabilizing the clot.

This determines that direct inhibition of Thrombin is a highly desirable target for prophylaxis and therapy of various Coagulation Disorders (CDs). Thrombin  has 3-sites for target activation:

Sites 1 and 2 are called Exosites and site-3 is called an active site. Exosite-1 is the Fibrin binding site of Thrombin and Exosite-2 serves as the Heparin-Binding Domain. The clotting pathway has traditionally been inhibited by using Heparin and Warfarin for treatment and prophylaxis of Coagulation Disorders (CDs).

Heparin inhibits free Thrombin by binding simultaneously to Exosites on Thrombin and Antithrombin, forming a Heparin-Thrombin-Antithrombin Complex. But Heparin cannot inhibit Fibrin bound Thrombin. Heparin can bind independently to Fibrin and Thrombin to form Fibrin-Heparin-Thrombin bridge.

It has been documented that both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are associated with variable anticoagulant effect and heparin induced thrombocytopenia (HIT) in around 3% cases. Warfarin acts as a Vitamin-K antagonist to inhibit formation of clotting factors (II, VII, IX, X). Vitamin-K antagonists have a number of shortcomings, including a delayed onset of action and interindividual variability in anticoagulant effect. Other drugs and foods have also been reported to alter anticoagulant effect of Vitamin-K antagonists. Anticoagulant treatment requires regular and frequent monitoring.

The effectiveness of heparin and warfarin in prophylaxis and treatment of various thromboembolitic disorders has been well established.  Effective use of these drugs comes with a steep cost of various side effects and problems like bleeding tendencies and immune thrombocytopenia. Parenteral administration needs hospitalization and constant monitoring during therapy.