Notes from the Video

What You're Going to Learn from This Video on Bleeding Disorders

Bleeding disorders can be very complicated!  There are lists of bleeding disorders and it can be almost impossible to remember everything. 

Today we're going to make learning bleeding disorders such as hemophilia and drugs like warfarin easy...you're goin to be a pro and crush the exams!

If you haven't had a chance to watch my video on coagulation cascades I would DEFINITELY check that page out before so you can have some nice baseline knowledge to build on!

We're going to cover many of the most important bleeding disorders and drugs including antiplatelet and anticoagulant agents. 

What are the most common bleeding disorders?

All of the. bleeding disorders have one thing in common: the inability to form or stabilize blood clots!

Von Willebrand disease (VWD): This is the most common inherited bleeding disorder, affecting up to 1% of the population. VWD is caused by a deficiency or dysfunction of von Willebrand factor, a protein that helps platelets stick to damaged blood vessels and also carries and stabilizes factor VIII in the blood.

Hemophilia A and B: Hemophilia A and B are caused by deficiencies in factor VIII and factor IX, respectively. These clotting factors are necessary for the formation of a stable blood clot, and individuals with hemophilia may experience prolonged bleeding after injury or surgery.

Platelet disorders: Disorders that affect platelet function, such as Glanzmann thrombasthenia or Bernard-Soulier syndrome, can cause bleeding symptoms similar to those seen in individuals with deficiencies in clotting factors.

Acquired bleeding disorders: These disorders are not inherited, but instead are caused by underlying medical conditions or medications that interfere with the blood clotting process. Examples include liver disease, vitamin K deficiency, and the use of anticoagulant medications.

What is Von Willebrand Disease?

There are three main types of Von Willebrand disease (VWD):

Type 1 VWD: This is the mildest form of the disease, characterized by a partial deficiency of von Willebrand factor (vWF). Individuals with type 1 VWD have vWF levels that are lower than normal, but still high enough to provide some protection against bleeding. Diagnosis of type 1 VWD is usually made by measuring vWF levels in the blood.

Type 2 VWD: Type 2 VWD is caused by a qualitative defect in vWF, meaning that the vWF protein is not functioning properly even though it may be present in normal or increased amounts. Type 2 VWD is further classified into several subtypes based on the specific defect in the vWF protein. Diagnosis of type 2 VWD typically involves specialized laboratory tests that evaluate vWF function.

Type 3 VWD: This is the most severe form of the disease, characterized by a complete deficiency of vWF.  Individuals with type 3 VWD may experience spontaneous bleeding, particularly in the joints and muscles, and are at high risk for severe bleeding after injury or surgery. Diagnosis of type 3 VWD is made by measuring vWF levels in the blood and confirming a complete deficiency of the protein.

In addition to these three main types, there are also several rare subtypes of VWD that are caused by genetic mutations in other genes that affect the production or function of vWF.

Diagnosis of VWD typically involves a combination of clinical evaluation, laboratory tests, and genetic testing.

Patients may undergo a medical history and physical exam to identify symptoms of bleeding or a family history of bleeding disorders.

Laboratory tests may include measuring levels of vWF antigen, vWF activity, and factor VIII activity in the blood, as well as specialized tests to evaluate vWF function.

Genetic testing may also be performed to identify mutations that cause VWD.

What is Hemophilia A?

Hemophilia A is an inherited bleeding disorder caused by a deficiency or dysfunction of clotting factor VIII. It affects mostly males and is characterized by prolonged bleeding after injury or surgery, spontaneous bleeding into muscles and joints, and bruising.

Diagnosis of hemophilia A is made through laboratory tests that measure levels of clotting factor VIII activity in the blood. Individuals with hemophilia A typically have significantly reduced levels of factor VIII activity compared to normal.

Management of hemophilia A in the perioperative period involves careful planning and coordination between the patient, their hematologist, and the surgical team. Patients with hemophilia A should be evaluated prior to surgery to determine their baseline clotting status and to develop a plan for perioperative management. This may involve preoperative administration of factor VIII concentrate to increase levels of clotting factor in the blood, as well as close monitoring of clotting status during and after surgery.

In some cases, alternative management strategies may be used to reduce bleeding risk, such as the use of tranexamic acid or other hemostatic agents.

Postoperative care may involve continued administration of factor VIII concentrate, monitoring of clotting status, and careful management of wound healing to prevent bleeding or hematoma formation.

Overall, the management of patients with hemophilia A in the perioperative period requires close coordination between the patient, their hematologist, and the surgical team to minimize bleeding risk and ensure optimal outcomes.

What are the anticoagulant medications and how do they work?

Heparin: Heparin works by binding to and activating antithrombin III, a natural anticoagulant in the body. The antithrombin III complex then inactivates clotting factors IXa, Xa, XIa, and XIIa.

Heparin is administered either intravenously or subcutaneously and is used to prevent and treat blood clots in a variety of situations, including deep vein thrombosis, pulmonary embolism, and during certain surgeries.

Warfarin: Warfarin works by inhibiting the synthesis of vitamin K-dependent clotting factors (factors II, VII, IX, and X) in the liver.

It is administered orally and is used to prevent and treat blood clots in a variety of situations, including atrial fibrillation, deep vein thrombosis, and pulmonary embolism.

What is warfarin induced skin necrosis?

Warfarin-induced skin necrosis (WISN) is a rare but serious side effect of warfarin therapy, which is characterized by the development of painful, non-inflammatory areas of skin necrosis, most commonly on the breasts, buttocks, thighs, and abdomen.

WISN usually occurs within the first few days to weeks of starting warfarin treatment or after a rapid increase in the dose of warfarin.

The exact mechanism of WISN is not completely understood, but it is believed to be related to warfarin-induced depletion of protein C, a natural anticoagulant in the body that inhibits blood clotting.

Warfarin inhibits the synthesis of vitamin K-dependent clotting factors, including factors II, VII, IX, and X, but it also inhibits the synthesis of protein C, which has anticoagulant activity. In patients with a deficiency of protein C, the inhibition of clotting factors by warfarin can lead to a procoagulant state, resulting in the formation of microthrombi in small blood vessels, which can ultimately cause tissue necrosis.

Patients who are at increased risk for WISN include those with protein C deficiency, those with a history of thrombosis or hypercoagulable states, and those with a genetic predisposition to clotting disorders.

Treatment of WISN includes discontinuation of warfarin therapy, administration of vitamin K, and supportive measures to manage pain and promote healing of the affected areas.

In some cases, protein C replacement therapy may be necessary. Prevention of WISN includes careful monitoring of the international normalized ratio (INR) in patients receiving warfarin therapy, particularly during the initial weeks of treatment and during periods of rapid dose escalation.

Direct oral anticoagulants (DOACs): DOACs are a newer class of anticoagulants that directly inhibit specific clotting factors.

The most commonly used DOACs are dabigatran (inhibits thrombin), apixaban, rivaroxaban, and edoxaban (all inhibit factor Xa). DOACs are administered orally and are used to prevent and treat blood clots in a variety of situations, including atrial fibrillation, deep vein thrombosis, and pulmonary embolism.

Low molecular weight heparin (LMWH): LMWH is a form of heparin that has a smaller molecular weight and a longer half-life than unfractionated heparin. LMWH works by binding to and activating antithrombin III, which inactivates clotting factors IXa, Xa, XIa, and XIIa. LMWH is administered subcutaneously and is used to prevent and treat blood clots in a variety of situations, including deep vein thrombosis and pulmonary embolism.

What are the antiplatelet agents?

There are a number of different antiplatelet agents and it is important to understand their mechanism of action as well as the indications and how to reverse them, especially in the setting up trauma.

Aspirin: Aspirin is a non-steroidal anti-inflammatory drug (NSAID) that works by irreversibly inhibiting the enzyme cyclooxygenase (COX), which is necessary for the production of thromboxane A2, a potent platelet activator.

Aspirin is administered orally and is used to prevent blood clots in a variety of situations, including heart attack, stroke, and peripheral arterial disease.

Clopidogrel: Clopidogrel is a thienopyridine derivative that works by irreversibly inhibiting the platelet adenosine diphosphate (ADP) receptor P2Y12, which is necessary for platelet activation and aggregation.

Clopidogrel is administered orally and is used to prevent blood clots in patients with acute coronary syndrome, peripheral arterial disease, and stroke.

Ticagrelor: Ticagrelor is a cyclopentyltriazolopyrimidine derivative that works by reversibly inhibiting the P2Y12 receptor. Ticagrelor is administered orally and is used to prevent blood clots in patients with acute coronary syndrome.

Prasugrel: Prasugrel is a thienopyridine derivative that works by irreversibly inhibiting the P2Y12 receptor. Prasugrel is administered orally and is used to prevent blood clots in patients with acute coronary syndrome who are undergoing percutaneous coronary intervention (PCI).

Dipyridamole: Dipyridamole is a phosphodiesterase inhibitor that works by increasing the levels of cyclic adenosine monophosphate (cAMP) in platelets, which inhibits platelet activation and aggregation. Dipyridamole is administered orally and is used in combination with aspirin to prevent blood clots in patients with a history of stroke or transient ischemic attack.

I hope you have enjoyed this article, there is definitely a lot of information but I hope this made it clear that understanding the coagulation cascades mades learning the bleeding disorders, anticoagulant and anti platelet medications easy!