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Coagulation Corner


Wednesday, January 3, 2018

Coagulation In The Elderly

Written By Donna Castellone, MS, MT (ASCP) SH | LinkedIn

Welcome to the new year- two thoughts - what will 2018 bring? And another year gone - what did I do in that year? For sure, we all have aged another year- and at times as daunting as that may seem, it is for sure better than the alternative! But it does make one think about aging- and what does that mean? What is considered old or elderly? (For me... it is a moving target, aka the closer I get to a number, the definition changes.) However, according the New York Times, someone between the ages of 69 and 71 is considered elderly. As we age, how does that impact hemostasis; are we more likely to bleed or thrombosis? How do comorbidities and medication impact these processes?


Bleeding in the elderly:

There are serious consequences of bleeding in the elderly and it is important to determine if this is caused by changes in their coagulation system. Most common types of bleeding occur in the gastrointestinal, respiratory and urogenital tracts. Several studies have demonstrated that factor XI, XII and AT increase in women and decrease in men, while X, VII, V and fibrinogen increased in both sexes. When looking at platelets, they were present in numbers but with slightly shortened lifespans, however all of the trends were small. Most of the bleeding disorders are the result of an underlying pathology.

Thrombocytopenia will cause bleeding when a platelet count falls below 50 x 109/1 but is frequently not seen until after the count has fallen below 20 x 109/1. Bleeding may occur at higher counts due to abnormal platelet function, or inadequate marrow production. Causes may be due to myelodysplasia, chronic or acute leukemia, certain drugs may cause a toxic effect on megakaryocytes and cause an aplastic anemia.

The presence of acquired inhibitors are more likely to be found in the elderly. These are autoantibodies directed against clotting factors, most commonly to factor VIII. These can be acquired due to malignancy, surgery, or may just be idiopathic. Bleeding is very severe and can be life threatening with mortality rates up to 22%. Patients present with large hematomas, gross hematuria, and cerebral hemorrhage. Patients are monitored by Bethesda titers and can by managed with factor replacement, immunosuppressive therapy and even chemotherapy.


Thrombosis in the elderly:

Thrombosis has been well recognized in the elderly population with noted increases in many coagulation factors. The concentration of fibrinogen, FV, FVIII, FVII, FIX, vWF, thrombin generation and platelet activation all increase with aging resulting in a procoagulant state. All of this may be due to ongoing inflammatory processes as reflected by the increase in acute phase reactants of FVIII and fibrinogen. Additionally there is an increase in acquired risk factors such as cancer, autoimmune disorders and diabetes which can cause abnormalities in hemostasis. The impact of aging can introduce confounding variables making diagnosis in the elderly challenging. The increase in d-dimer as one ages supports the using of age adjusted levels. Also, since vWF increases with age, it can appear that patients with type 1 vWD appear to normalize and can make treatment difficult.

There has also been noted changes in the fibrinolytic system. Plasminogen has been noted to be decreased in those 75 years or older, as well as a slight decrease in women. Plasminogen activator inhibitor(PAI-1) has also been increased and is an acute phase reactant that is influenced by several cytokines and hormones and may play a role in hypercoagulability.


Anticoagulation in the elderly:

Anticoagulation in elderly patients is a challenge since they are at a risk for thrombosis, but also are at a high hemorrhagic risk but are more likely to require anticoagulation therapy at some point. The risk benefit ratio in this population regarding anticoagulation is key in decision making. There are several considerations in the elderly that need to be taken into account. These include renal insufficiency, and the pharmacodynamics of anticoagulants in particular vitamin K antagonists. Other issues include concomitant medication and patient comorbidities, age related decrease in body weight, alterations in liver function and a reduction of muscle mass.

The most common indication for anticoagulation in this population is due to atrial fibrillation and the treatment and prevention of DVT and PE. The majority of VTE occurs in patients over 70.

Warfarin is used in these cases, but require frequent and careful monitoring of the INR used to prevent bleeding however it is underutilized in the elderly. Even though the elderly are at a higher risk for bleeding, the benefit for stroke reduction exceeds the risk. However, it is underutilized in this population. The direct oral anticoagulants such as dabigatran, rivaroxaban and apixaban have been determined to be at least as effective as warfarin in preventing strokes however appear to reduce the risk of intracranial hemorrhage.

Dabigatran is dosed twice daily, which may be problematic, since elderly patients may not remember to take them, or take one to save money. It is also dependent on renal excretion and contraindicated in patients with severe renal disease. Rivaroxaban is less impacted by renal disease since it is metabolized by the liver. The risk of IC bleeding is less than warfarin, but increased with other types of bleeding. It is dosed once/day. The DOAC's have been determined to be at least as effective as warfarin in reducing the risk of stroke and appear to be safer than warfarin in this population and do not require monitoring. However, they are more expensive, the overall cost of their utilization in the management and prevention is unclear.


Conclusion:

The elderly population is increasing with the life expectancy in 2040 to be between 89-94 years of age. Increased awareness and treatment strategies will continue to evolve.

With that being said, as we all march to the new year, I hope that yours is filled with happiness and good health for you and your family. All the best in 2018!





 




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