What are the causes of elevated Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and International Normalized Ratio (INR)?

From the Guidelines

Elevated PT, PTT, and INR are commonly caused by several conditions, including anticoagulant medications, liver disease, vitamin K deficiency, and disseminated intravascular coagulation (DIC), as well as other factors such as massive blood transfusions, severe sepsis, and inherited clotting disorders. The most common causes of elevated coagulation parameters include:

• Anticoagulant medications such as warfarin, heparin, and direct oral anticoagulants like apixaban, rivaroxaban, dabigatran, and edoxaban, which can increase the risk of bleeding and elevate PT, PTT, and INR 1
• Liver disease, such as cirrhosis, hepatitis, and alcoholic liver disease, which can lead to elevated coagulation times due to decreased production of clotting factors by the liver 1
• Vitamin K deficiency, which can increase these values since vitamin K is essential for synthesizing several clotting factors, and can be caused by malnutrition, malabsorption syndromes, or prolonged antibiotic use
• Disseminated intravascular coagulation (DIC), a serious condition where clotting factors are consumed throughout the body, typically elevates all three parameters Other causes include:
• Massive blood transfusions, which can dilute clotting factors and lead to elevated coagulation parameters
• Severe sepsis, which can cause coagulopathy and elevate PT, PTT, and INR
• Certain cancers, particularly leukemias, which can increase the risk of bleeding and elevate coagulation parameters
• Inherited clotting disorders, such as hemophilia and von Willebrand disease, which can primarily affect PTT and increase the risk of bleeding When encountering elevated coagulation parameters, it's essential to consider the patient's medication history, underlying medical conditions, and clinical presentation to determine the cause and appropriate management, as recommended by the American Heart Association and American Stroke Association 1.

From the FDA Drug Label

The following factors, alone or in combination, may be responsible for INCREASED PT/INR response: ENDOGENOUS FACTORS: blood dyscrasias — diarrhea hyperthyroidism see CONTRAINDICATIONS elevated temperature poor nutritional state cancer hepatic disorders steatorrhea collagen vascular disease infectious hepatitis vitamin K deficiency congestive heart failure jaundice EXOGENOUS FACTORS: Potential drug interactions with warfarin sodium tablets are listed below by drug class and by specific drugs.

The causes of elevated PT, PTT, and INR include:

• Endogenous factors:
  • Blood dyscrasias
  • Diarrhea
  • Hyperthyroidism
  • Elevated temperature
  • Poor nutritional state
  • Cancer
  • Hepatic disorders
  • Steatorrhea
  • Collagen vascular disease
  • Infectious hepatitis
  • Vitamin K deficiency
  • Congestive heart failure
  • Jaundice
• Exogenous factors:
  • Drug interactions with warfarin sodium tablets, including:
    • 17-Alkyl Penicillins
    • Gout Treatment Agents
    • Testosterone Derivatives
    • Fluoroquinolones
    • Dextran
    • Activator (t-PA)
    • Dextrothyroxine
    • Moricizine hydrochloride
    • Tolbutamide
    • Diazoxide
    • Nalidixic acid
    • Tramadol
    • Diclofenac
    • Naproxen
    • Trimethoprim/sulfamethoxazole
    • Dicumarol
    • Neomycin
    • Urokinase
    • Diflunisal
    • Norfloxacin
    • Valdecoxib
    • Disulfiram
    • Ofloxacin
    • Valproate
    • Doxycycline
    • Olsalazine
    • Vitamin E
    • Erythromycin
    • Omeprazole
    • Zafirlukast
    • Esomeprazole
    • Oxandrolone
    • Zileuton
    • Ethacrynic acid
    • Oxaprozin
    • Ezetimibe
    • Oxymetholone
    • Fenofibrate
    • Pantoprazole 2

From the Research

Causes of Elevated PT, PTT, and INR

• Liver disease: Studies have shown that liver disease can cause elevated PT, PTT, and INR due to decreased production of vitamin K-dependent clotting factors 3.
• Use of anticoagulant medications: The use of anticoagulant medications such as warfarin or heparin can cause elevated PT, PTT, and INR 4.
• Hemodialysis: Patients on hemodialysis are also at risk of elevated PT, PTT, and INR 4.

Predicting Abnormal Coagulation

• Certain risk factors can predict abnormal coagulation, including the use of anticoagulant medications, hemodialysis, and liver disease 3, 4.

Laboratory Tests

• Prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) are commonly used laboratory tests to evaluate coagulation 3, 4.
• Elevated PT, PTT, and INR can indicate a coagulopathy, which can be caused by various factors, including liver disease, use of anticoagulant medications, and hemodialysis 3, 4.