Hypocoagulable conditions, also known as bleeding disorders or bleeding diatheses, are a diverse group of diseases that result in abnormal hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis. Hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis is the innate, stepwise process resulting in bleeding cessation from a damaged blood vessel. Physiologic hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis is dependent on the integrity of endothelial cells and subendothelial Subendothelial Membranoproliferative Glomerulonephritis matrix, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, and coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis. The hypocoagulable states result from abnormalities in one or more of these contributors, resulting in ineffective thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus and bleeding.
Last updated: 8 Apr, 2021
Hypocoagulable conditions, also known as bleeding disorders or bleeding diatheses, are a diverse group of diseases that result in abnormal hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis and increased bleeding risk.
Physiologic hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis is dependent on normal structure and function of:
The following is a summary of the process:
Formation of the temporary hemostatic plug:
The disrupted endothelial surface exposes
von Willebrand Factor
von Willebrand factor
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in von Willebrand diseases is due to the deficiency of this factor.
Hemostasis (vWF) to the passing blood.
Platelets
Platelets
Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm.
Platelets: Histology
bind
BIND
Hyperbilirubinemia of the Newborn to the vWF via their GpIb
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors and are activated.
Platelet activation
Platelet activation
A series of progressive, overlapping events, triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
Hemostasis
triggers
Triggers
Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) them to secrete
adenosine
Adenosine
A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
Class 5 Antiarrhythmic Drugs diphosphate (ADP), which stimulates the expression of the GpIIb/IIIa
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors on the
platelets
Platelets
Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm.
Platelets: Histology. The GpIIb/IIIa
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors
bind
BIND
Hyperbilirubinemia of the Newborn to
fibrinogen
Fibrinogen
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Hemostasis, which is able to
bind
BIND
Hyperbilirubinemia of the Newborn a platelet on each end, causing
platelets
Platelets
Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm.
Platelets: Histology to aggregate. As more
platelets
Platelets
Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm.
Platelets: Histology are bound to one another, the
platelet plug
Platelet plug
Hemostasis is generated. As the
coagulation cascade
Coagulation cascade
The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot.
Hemostasis is activated,
thrombin
Thrombin
An enzyme formed from prothrombin that converts fibrinogen to fibrin.
Hemostasis converts the weaker
fibrinogen
Fibrinogen
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Hemostasis into the stronger
fibrin
Fibrin
A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot.
Rapidly Progressive Glomerulonephritis, creating a much more stable clot.
Overview of the
coagulation cascade
Coagulation cascade
The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot.
Hemostasis
a: activated form
PF3: platelet factor 3 (
phospholipids
Phospholipids
Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.
Lipid Metabolism)
Assessing the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis
Image by Lecturio.The following conditions can lead to a hypocoagulable state.
Inherited conditions | Acquired conditions | |
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Vessel wall disorders |
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Platelet disorders |
|
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Coagulation disorders | Hemophilias A, B, and C |
|
Mixed disorders | Von Willebrand disease Von Willebrand disease Von Willebrand disease (vWD) is a bleeding disorder characterized by a qualitative or quantitative deficiency of von Willebrand factor (vWF). Von Willebrand factor is a multimeric protein involved in the plate adhesion phase of hemostasis by forming a bridge between platelets and damaged portions of the vessel wall. Von Willebrand Disease | Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation |
Medications |
|
A hypocoagulable state may present in the following ways:
Cutaneous bleeding | Mucosal bleeding Mucosal bleeding Chédiak-Higashi Syndrome | Internal bleeding | Onset of bleeding after trauma | |
---|---|---|---|---|
Platelet disorders | âś“ | âś“ | – | Early (immediately) |
Vessel disorders | ✓ | – | – | – |
Disorders of the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis | – | – | ✓ | Late (minutes to hours) |
Bleeding disorders may stem from abnormalities of the vessel wall.
Inherited disorders of the connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology matrix can cause vascular fragility, leading to frequent vessel injury.
Hereditary hemorrhagic telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency
Image: “Clinical manifestations of HHT” by Latino et al AL Amyloidosis. License: CC BY 4.0, cropped by Lecturio.The following acquired conditions may lead to vascular fragility and increase vessel injury:
Inherited disorders:
Acquired conditions: