Hemostasis and the coagulation system represent a homeostatic balance between factors encouraging clotting and factors encouraging clot dissolution. The first reaction of the body to active bleeding is blood vessel constriction. In small vessel injury this may be enough to stop bleeding. In large vessel injury, hemostasis is required to form a clot that will durably plug the hole until healing can occur. The primary phase of the hemostatic mechanism involves platelet aggregation to blood vessel. Next, secondary hemostasis occurs. The first phase of reactions is called the intrinsic system. Factor XII and other proteins form a complex on the subendothelial collagen in the injured blood vessel. Through a series of reactions, activated factor XI (XIa) is formed and activates factor IX (IXa). In a complex formed by factors VIII, IX, and X, activated X (Xa) is formed.
At the same time the extrinsic system is activated and a complex is formed between tissue thromboplastin (factor III) and factor VII. Activated factor VII (VIIa) results. VIIa can directly activate factor X. Alternatively, VIIa can activate IX and X together.
The final step is a common pathway in which prothrombin is converted to thrombin on the surface of the aggregated platelets. The main purpose of thrombin is to convert fibrinogen to fibrin, which is then polymerized into a stable gel. Factor XIII crosslinks the fibrin polymers to form a stable clot.
Almost immediately three major activators of the fibrinolytic system act on plasminogen, which had previously been absorbed into the clot, to form plasmin. Plasmin degenerates the fibrin polymer into fragments that are cleared by macrophages.
The PTT measures the clotting ability of factors I (fibrinogen), II (prothrombin), V, VIII, IX, X, XI, and XII. Since both PTT and INR are evaluating different coagulation factors, when both PTT and INR tests are used together almost all of the hemostatic abnormalities can be examined. PTT is prolonged if any of the stated factors is found in abnormal levels, prolonged time caused by these factors can be noticed in the cases of hemophilia A and B or consumptive coagulopathy. Vitamin K participate in the synthesis of factors II, IX, and X, which means that vitamin K deficiency or biliary obstruction (which plays a rule in producing vitamin K), may reduce factors II, IX, or X levels causing prolong the PTT. Hepatocellular Diseases will also increase the PTT since the liver is where coagulation factors are made.
Heparin has been found to inactivate prothrombin (factor II) and to prevent the formation of thromboplastin. These actions prolong the intrinsic clotting pathway for approximately 4 to 6 hours after each dose of heparin. Therefore heparin is capable of providing therapeutic anticoagulation. The appropriate dose of heparin can be monitored by the PTT. PTT test results are given in seconds along with a control value. The control value may vary slightly from day to day because of the reagents used.
Recently activators have been added to the PTT test reagents to shorten normal clotting time and provide a narrow normal range. This shortened time is called the activated PTT. The normal aPTT is 30 to 40 seconds. Desired ranges for therapeutic anticoagulation are 1.5 to 2.5 times normal (e.g., 70 seconds). The aPTT specimen should be drawn 30 to 60 minutes before the patient’s next heparin dose is given. If the aPTT is less than 50 seconds, therapeutic anticoagulation may not have been achieved and more heparin is needed. An aPTT greater than 100 seconds indicates that too much heparin is being given; the risk for serious spontaneous bleeding exists when the aPTT is this high. The effects of heparin can be reversed by the parenteral administration of 1 mg of protamine sulfate for every 100 units of the heparin dose.
Heparin’s effect, unlike that of warfarin, is immediate and short lived. When a thromboembolic episode (e.g., pulmonary embolism, arterial embolism, thrombophlebitis) occurs, immediate and complete anticoagulation is most rapidly and safely achieved by heparin administration. This drug is often given during cardiac and vascular surgery to prevent intravascular clotting during clamping of the vessels. Often small doses of heparin (5000 units subcutaneously every 12 hours) are given to prevent thromboembolism in high-risk patients. This dose alters the PTT very little, and the risk for spontaneous bleeding is minimal.
Normal aPTT Levels
The Normal aPTT Levels range between 30 and 40 seconds in a healthy person. In patients who receive Anticoagulant Therapy, the Normal aPTT Levels would range 1.5 to 2.5 times the value of the control period. The same rule also applies on the Normal PTT Levels of patients who receive Anticoagulant Therapy.
The Normal PTT Levels range between 60 and 70 seconds.
Causes of High aPTT Levels
- Congenital Clotting Factor Deficiencies (e.g., von Willebrand Disease, Hemophilia, Hypofibrinogenemia): These hereditary illnesses are associated with very little, if any, of the respective clotting factors. As a result, the PTT is prolonged.
- The liver makes most of the clotting factors. For synthesis of some of those clotting factors, vitamin K is required. In patients with Vitamin K deficiency or Cirrhosis of the Liver the clotting factors of the intrinsic system and common pathways are inadequate in quantity. As a result, the PTT is prolonged.
- Disseminated Intravascular Coagulation (DIC): Key clotting factors involved in the intrinsic system are consumed.
- Heparin Administration: Heparin inhibits the intrinsic system at several points. As a result, the PTT is prolonged.
- Coumarin Administration: Although coumarin has a greater impact on the prothrombin time, it does inhibit the function of factors II, IX, and X. As a result, the PTT is prolonged.
Causes of Low aPTT Levels
- Early stages of Disseminated Intravascular Coagulation (DIC): Circulating procoagulants exist in the early stages of DIC. These act to shorten or decrease the PTT.
- Extensive Cancer (e.g., Ovarian, Pancreatic, Colon): The pathophysiology of this association is not well known.