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Related Concept Videos

Disorders of Hemostasis01:24

Disorders of Hemostasis

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Hemostasis, the process that stops bleeding after a blood vessel injury, is crucial for maintaining the integrity of the circulatory system. However, disorders of hemostasis can disrupt this delicate balance, leading to either excessive clotting or bleeding. These disorders can be broadly classified into thromboembolic disorders and bleeding disorders.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
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Structure and Function of Platelets01:18

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The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
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Formation of the Platelet Plug01:22

Formation of the Platelet Plug

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The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
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Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

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Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
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Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

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Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
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Disorders of Erythrocytes01:27

Disorders of Erythrocytes

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Disorders of erythrocytes, or red blood cells (RBCs), include a range of conditions affecting their number, shape, or function.
Erythrocyte disorders can be broadly categorized into two main types: anemic and polycythemic conditions.
A low oxygen-carrying capacity of the blood due to the loss, lower production, or destruction of erythrocytes is termed anemia. Hemorrhagic anemia, for example, occurs when bleeding from an external wound or internal ulcer reduces erythrocyte counts.
On the other...
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Update on the inherited platelet disorders.

Michele P Lambert1

  • 1The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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Summary

Recent advances in next-generation sequencing have identified novel genes and mechanisms underlying inherited platelet disorders, improving our understanding of these conditions. Continued research is crucial for diagnosing and potentially treating these rare bleeding disorders.

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Area of Science:

  • Hematology
  • Genetics
  • Molecular Biology

Background:

  • Inherited platelet disorders are a diverse group of rare bleeding conditions.
  • Understanding their molecular basis has been significantly advanced by new genetic technologies.

Purpose of the Study:

  • To review recent discoveries in inherited platelet disorders.
  • To highlight novel genes and molecular mechanisms identified.
  • To focus on newly described platelet disorders.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of next-generation sequencing data for novel gene discovery.
  • Clinical phenotyping of patients with platelet disorders.

Main Results:

  • Identification of mutations in PRKACG associated with severe macrothrombocytopenia.
  • Discovery of RUNX1 and FLI1 mutations in mild inherited platelet function disorders.
  • Characterization of CalDAG-GEFI mutations causing severe bleeding phenotypes.

Conclusions:

  • Ongoing research continues to uncover new genetic causes for platelet disorders.
  • Whole exome/genome sequencing offers potential for patient evaluation but requires cautious interpretation in clinical settings.
  • Further studies are needed to validate variant interpretations outside of research.