Disorders of Hemostasis, Free CME Quiz, Earn Free CME Credit

The correct answer is:

Mostly a platelet problem: immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), von Willebrand disease, anti-thrombotic medications (e.g. aspirin, clopidogrel, prasugrel, ticagrelor).

Educational Objective:

Assign clinical bleeding presentations to their underlying pathology.

Key Point:

Knowing which end product (platelets, fibrin, or both) is likely to be compromised can help with initial management decisions in a bleeding patient with coagulopathy.

Explanation:

Platelet Problems: 

The following abnormal bleeding problems are due to a lack of functional platelets:

• immune thrombocytopenic purpura (ITP),
  
• thrombotic thrombocytopenic purpura (TTP),
  
• hemolytic-uremic syndrome (HUS),
  
• Drug-induced thrombocytopenias (DIT),
  
• HELLP Syndrome of pregnancy (hemolysis, elevated liver enzymes, low platelets), and
  
• von Willebrand disease.
  

Significant bleeding due to compromised platelet function can often be managed with transfusions of platelet and/or vWF (exception: in condition with thrombocytopenia accompanied by thrombosis, the patient should not receive platelet transfusions because the new platelets will add to the pathological thrombosis).

Pearl:

The von Willebrand Factor (vWF) bridges between the thrombosis system and clotting cascade system, helping both platelets to clump properly (see figure) and Factor VIII of the clotting system to optimally support the production of fibrin. 

Fibrin Problems:

The coagulopathies that lead to an inadequate fibrin meshwork are much shorter than that of platelet problems; however, the list of treatments is much longer than it is for platelet problems. The following coagulopathies result in insufficient fibrin: 

• the hemophilias,
  
• early liver disease, and
  
• over-anticoagulation with anticoagulants (e.g. heparin, the new oral anticoagulants, coumadin).
  

Therapeutically raising fibrin levels is possible with the following products: (note that none of the below products will raise platelet levels):

• fresh frozen plasma: directly increases levels of fibrinogen (precursor to fibrin) AND delivers all clotting factors;
  
• isolated fibrinogen: directly increases levels of fibrinogen (precursor to fibrin);
  
• tranexamic acid: prevents the breakdown of already formed fibrin;
  
• vitamin K:  supports  extrinsic clotting pathway (dysfunctional in liver disease, coumadin over-anticoagulation), which will in turn stimulate the common clotting pathway which will in turn produce more fibrin (end-product of common pathway);
  
• prothrombin complex concentrate (PCC): provides the clotting factors of the extrinsic pathway to overcome e.g. the effects of coumadin, which in turn stimulates the patient’s own common pathway, which produces  fibrin;
  
• protamine (heparin antidote) or idarucizumab (Dabigatran antidote): to reverse medication-induced blockage of the common clotting pathway. 
  
  

Combined Platelet/Fibrin Problem:

The following diseases are a combination platelet/coagulation problem: 

• disseminated intravascular coagulopathy (DIC),
  
• end-stage liver disease,
  
• Von Willebrand disease, and
  
• trauma with exsanguination that requires > 10 units of packed red blood cells (PRBCs) (the exsanguinating patient is obviously not only losing red blood cells but also platelets and coagulation factors).
  

Mixed platelet/coagulation problems usually require a combination of one of the above fibrin-supporting products and platelet transfusions.

Figure:

Role of von Willebrand Factor in aiding platelets with aggregation and adhesion to result in thrombosis