April 30, 2021

Bleeding Disorders

Authors: Payal Chawla1
Affiliations: 1Universitätsklinikum Bonn


Under normal physiological conditions, a balance between clotting and bleeding is always maintained. However, pathological conditions can disrupt this balance and lead to hemorrhagic or thrombotic complications a.k.a “Coagulopathy”. Coagulopathy is a condition in which the blood clot formation is impaired and can be classified as disorders that can cause abnormal bleeding or abnormal clotting. This abnormality of the coagulation cascade can affect primary hemostasis, coagulation pathways and the fibrinolytic system.

CPrimary Haemostasis is a mechanism that arises from the interactions between platelets, wall of the blood vessel and adhesive proteins, which helps to form the initial “platelet plug”. A defect in this mechanism is due to either the vessel wall abnormality or the number and level of quality of platelets (Fig.1).


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Figure 1: Classification of disorders related to primary hemostasis based on the vessel wall quality, platelet number and function

 

Coagulation pathways have proteins termed “Coagulation proteins” and are the core components of the coagulation system. They play an active role in the formation of a blood clot. A variety of disorders stem from the defect in the coagulation cascade and can be classified as coagulation disorders and further classified as acquired or inherited (Fig. 2).

Fibrinolytic system is activated in parallel to the coagulation cascade. It functions to limit the size of the blood clot by a process called Fibrinolysis. Disorders related to the abnormal functioning of the fibrinolytic system are rare. An increased rate of fibrinolysis can cause an increased tendency to bleed since it deters the clot formation (Fig 3.) while a decrease rate of fibrinolysis can lead to Thromboembolism where a blood clot breaks loose, is carried into the blood stream and can plug another blood vessel.


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Fig. 2: Classification of disorders related to the coagulation pathway differentiated to acquired / inherited bleeding disorders and acquired/ inherited thrombotic disorders

 

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Fig. 3: Effects of abnormal fibrinolysis. Increase in fibrinolysis (blood clot breakdown) can lead to bleeding and a decrease in the same can loosen the blood (thromboembolism) clot posing a risk of plugging a different blood vessel

 

The frequency of occurrence and clinical symptoms of bleeding disorders vary around the world. If two different individuals are affected with the same type of bleeding disorder the symptoms may vary drastically. Subsequently, these symptoms could occur at birth or later in life and range from minor post-traumatic to severe episodes. It is important to investigate the disorders and can be done through screening tests for coagulation, which includes measuring the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). Additional method of investigation is via molecular diagnosis where the mutation in the genes that encode for specific corresponding coagulation factors can be identified.

In summary, bleeding disorders need to be evaluated based on the special aspects for each disorder and cannot be grouped into a single classification. The delicate balance between the bleeding and blood clot formation mechanisms needs to be maintained physiologically. An imbalance of the same could predispose to an array of bleeding disorders.

References:

[1] Roberta Palla, Flora Peyvandi and Amy D. Shapiro. Rare bleeding disorder: diagnosis and treatment; 2015 DOI 10.1182/blood-2014-08-532820
[2] Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth 2014;58:515-23
[3] Crit Rev Biochem Mol Bio. 2015;50(4): 326-336. Doi:10.2109/10409238.2015.1050550
[4] Earl W. Davie and Kazuo Fujikawa Basic mechanisms in blood coagulation. Annu. Rev,Biochem 1975.44:799-829