From the Guidelines
Elevated PT in children is a complex condition that requires prompt evaluation and management, with a focus on determining the underlying cause, which could be inherited thrombophilia, age, CVAD, disease, trauma, long-term inactivity, or drugs, as identified in 94% of children with VTE 1. The initial approach should involve a thorough diagnostic workup, including liver function tests, complete blood count, and additional coagulation studies like PTT and fibrinogen.
- The elevated PT reflects decreased production of clotting factors II, V, VII, and X, which are vitamin K-dependent or synthesized by the liver.
- In cases of vitamin K deficiency, administer vitamin K1 (phytonadione) at 0.5-1 mg/kg IV, IM, or subcutaneously, with a maximum dose of 10 mg.
- For active bleeding with significantly prolonged PT, fresh frozen plasma (FFP) at 10-15 mL/kg may be necessary.
- The use of direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban may be considered for the treatment of VTE in pediatric patients, with rivaroxaban being recently approved for pediatric VTE treatment in several countries, including the United States, Europe, Japan, and China 1. The most effective treatment approach should be based on the underlying cause of the elevated PT, and may involve a combination of vitamin K supplementation, FFP, and DOACs, with ongoing monitoring of PT measurements to assess treatment effectiveness 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 elevated temperature poor nutritional state cancer hepatic disorders steatorrhea collagen vascular disease infectious hepatitis vitamin K deficiency congestive heart failure jaundice
The elevated PT in children may be caused by various factors, including:
- 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, and jaundice. It is essential to monitor the patient's response with additional PT/INR determinations when initiating or discontinuing medications, including botanicals, to ensure safe and effective anticoagulation therapy 2.
From the Research
Elevated PT in Children
- Elevated PT (prothrombin time) in children can be caused by various factors, including vitamin K deficiency 3
- Vitamin K deficiency can lead to a depletion of liver stores of phylloquinone, decreased plasma levels of vitamin K1, and increased levels of K1 epoxide, resulting in a prolongation of the APTT, PT, and thrombotest 3
- A study found that coagulopathy was identified in 20% of children referred for abnormal PT and/or PTT, and factors predictive of a bleeding risk were a positive family history of bleeding and a positive personal history of bleeding 4
- Vitamin K replacement is a cornerstone of management for warfarin-associated coagulopathy, and daily vitamin K supplementation can help regulate international normalized ratios in difficult-to-control patients 5
- In children with elevated PT, a normal PT and/or PTT on repeat testing has a negative predictive value of more than 95% in the absence of a personal or family history of bleeding 4
Vitamin K Deficiency
- Vitamin K deficiency can occur at any age, but the major public health problem is related to the prevention of early, classic, and late hemorrhagic disease of the newborn (HDN) 3
- A single dose of oral or parenteral vitamin K can prevent classic HDN, but the most effective way to prevent early HDN is by giving large doses to the mother prior to delivery 3
- Vitamin K is also involved in the maturation of proteins that play different roles, including the modulation of the calcification of connective tissues, and research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases 6
Diagnosis and Management
- The workup for prolonged PT and activated partial thromboplastin time (PTT) should be performed in a timely and cost-effective manner, and the complete laboratory assessment of the coagulation state has not been standardized 4
- A practical approach to pediatric patients referred with an abnormal coagulation profile includes determining which clinical and laboratory data are most predictive of a coagulopathy and formulating the most efficient strategy to reach a diagnosis 4