Disseminated Intravascular Coagulation (DIC): A microangiopathy

Table of Content

Introduction

Causes of DIC

How does fibrinolysis and microangiopathy occur in disseminated intravascular coagulation (DIC)?

Clinical features of disseminated intravascular coagulation (DIC)

Laboratory investigations for disseminated intravascular coagulation (DIC)

How is disseminated intravascular coagulation (DIC) treated and managed?

Key Points of DIC

References

Introduction

Disseminated intravascular coagulation (DIC) is a complex and often life-threatening disorder in which widespread blood clotting occurs throughout the body. This excessive clotting can lead to the consumption of clotting factors and platelets, resulting in a bleeding diathesis. The hallmark of DIC is the activation of both the coagulation and fibrinolysis. This activation leads to the formation of microthrombi (small blood clots) in the microvasculature. The microthrombi can obstruct blood flow and damage small blood vessels causing microangiopathy. The consumption of clotting factors and platelets can lead to bleeding, which can manifest as bruises, petechiae (small red spots on the skin), or even major hemorrhage.

Causes of disseminated intravascular coagulation (DIC)

DIC can be triggered by a variety of underlying conditions. Some of the most common causes of DIC include:

• Sepsis: Sepsis is a life-threatening condition that occurs when the body’s immune system overreacts to an infection. Sepsis is a major cause of DIC, as the inflammatory response can trigger the activation of both the coagulation and fibrinolytic systems.
• Trauma: Trauma can cause DIC by releasing tissue factors that activate the coagulation cascade. DIC is a common complication of major trauma, such as car accidents, falls, and gunshot wounds.
• Cancer: Cancer can cause DIC by releasing substances that activate the coagulation cascade. Certain types of cancer, such as leukemia, are more likely to be associated with DIC.
• Obstetric complications: Obstetric complications, such as abruptio placentae (premature separation of the placenta from the uterus) and amniotic fluid embolism (a rare but serious condition in which amniotic fluid enters the bloodstream), can cause DIC.
• Other medical conditions: A number of other medical conditions can cause DIC, including:
  • Liver disease
  • Hemolytic uremic syndrome (HUS)
  • Thrombotic thrombocytopenic purpura (TTP)
  • Snakebites
  • Certain medications

In some cases, the cause of DIC is unknown. This is known as idiopathic DIC.

DIC can also be caused by a number of medications, including:

• Asparaginase
• L-asparaginase
• Alteplase
• Streptokinase
• Urokinase

How does fibrinolysis and microangiopathy occur in disseminated intravascular coagulation (DIC)?

Fibrinolysis and microangiopathy

Fibrinolysis is the process by which blood clots are broken down. In DIC, fibrinolysis is activated in an attempt to remove the microthrombi that are forming throughout the body. However, the excessive activation of fibrinolysis can lead to the degradation of fibrinogen and other clotting factors, which can further exacerbate the bleeding diathesis.

Microangiopathy is the damage to small blood vessels. In DIC, microangiopathy is caused by the formation of microthrombi in the microvasculature. The microthrombi can obstruct blood flow and damage the vessel walls. This can lead to a number of complications, such as organ dysfunction, bleeding, and death.

Pathophysiology of disseminated intravascular coagulation (DIC)

The pathophysiology of DIC is complex and not fully understood. However, it is believed that DIC is caused by the activation of both the coagulation and fibrinolytic systems. This activation can be triggered by a variety of underlying conditions, such as sepsis, trauma, cancer, and obstetric complications.

The activation of the coagulation system leads to the formation of thrombin. Thrombin is an enzyme that converts fibrinogen into fibrin. Fibrin is a protein that forms the structural basis of blood clots. The formation of fibrin can lead to the development of microthrombi throughout the body.

The activation of the fibrinolytic system leads to the breakdown of fibrin. This can help to prevent the growth of microthrombi. However, the excessive activation of fibrinolysis can lead to the degradation of fibrinogen and other clotting factors, which can further exacerbate the bleeding diathesis.

The following are some of the key events in the pathophysiology of DIC:

1. Initiation: The coagulation cascade is activated by a variety of triggers, such as tissue factor, thrombin, and activated protein C.
2. Propagation: The activated coagulation factors generate thrombin. Thrombin converts fibrinogen into fibrin.
3. Clot formation: Fibrin forms a mesh that traps red blood cells, platelets, and other blood cells. This forms a blood clot.
4. Fibrinolysis: The fibrinolytic system is activated. Plasmin is generated from plasminogen. Plasmin breaks down fibrin.
5. Consumption: Clotting factors and platelets are consumed in the process of clot formation. This can lead to a deficiency of clotting factors and platelets.
6. Bleeding: The deficiency of clotting factors and platelets can lead to bleeding.

Clinical features of disseminated intravascular coagulation (DIC)

The clinical features of disseminated intravascular coagulation (DIC) can vary depending on the severity of the condition. However, some of the most common clinical features of DIC include:

• Bleeding: Bleeding is a common clinical feature of DIC. This can manifest as bruises, petechiae (small red spots on the skin), gingival bleeding, epistaxis (nosebleeds), or even major hemorrhage.
• Thrombosis: Thrombosis is another common clinical feature of DIC. This can manifest as deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, or myocardial infarction (heart attack).
• Microvascular dysfunction: Microvascular dysfunction can lead to a variety of symptoms, such as organ dysfunction, shock, and death.
• Fever: Fever is a common symptom of DIC. This is likely due to the release of inflammatory cytokines.
• Hypotension (low blood pressure): Hypotension is a common symptom of DIC. This is likely due to the loss of blood volume and the effects of inflammatory cytokines.
• Tachycardia (rapid heart rate): Tachycardia is a common symptom of DIC. This is likely due to the body’s attempt to compensate for the loss of blood volume.
• Oliguria (decreased urine output): Oliguria is a common symptom of DIC. This is likely due to the effects of inflammatory cytokines on the kidneys.
• Confusion: Confusion is a common symptom of DIC. This is likely due to the effects of inflammatory cytokines on the brain.
• Coma: Coma is a rare but serious complication of DIC. This is likely due to the effects of inflammatory cytokines on the brain.

Laboratory investigations for disseminated intravascular coagulation (DIC)

The laboratory investigations for disseminated intravascular coagulation (DIC) are aimed at assessing the activation of both the coagulation and fibrinolytic systems. Some of the most common laboratory investigations for DIC include:

• Complete blood count: Anemia and thrombocytopenia. Thrombocytopenia, a decrease in platelet count, is a hallmark feature of DIC.
• Peripheral blood smear: Presence of schistocytes and thrombocytopenia. Schistocytes are fragmented red blood cells with a helmet-shaped appearance. They are a consequence of mechanical shearing forces caused by microthrombi formation in the microvasculature. The presence of schistocytes in the peripheral blood smear suggests DIC.
• Prothrombin time (PT): The PT measures the time it takes for blood to clot. A prolonged PT can be indicative of a deficiency in clotting factors II, V, VII, or X.
• Activated partial thromboplastin time (APTT): The APTT measures the time it takes for blood to clot. A prolonged APTT can be indicative of a deficiency in clotting factors VIII, IX, XI, or XII.
• International normalized ratio (INR): The INR is a standardized measure of the PT. The INR is used to monitor the effects of warfarin therapy.
• D-dimer: D-dimer is a fragment of fibrin that is produced during the breakdown of blood clots. An elevated D-dimer level can be indicative of increased fibrinolytic activity.
• Fibrinogen: Fibrinogen is a clotting factor that is essential for the formation of blood clots. A decreased fibrinogen level can be indicative of consumption of clotting factors.
• Platelet count: Platelets are blood cells that are involved in the clotting process. A decreased platelet count can be indicative of consumption of platelets.
• Fibrin degradation products (FDPs): FDPs are fragments of fibrin that are produced during the breakdown of blood clots. An elevated FDP level can be indicative of increased fibrinolytic activity.

In addition to these laboratory investigations, other tests may be ordered to assess the underlying cause of DIC. For example, a blood culture may be ordered to rule out sepsis.

The interpretation of laboratory investigations for DIC can be complex. A combination of abnormal test results is typically needed to make a diagnosis of DIC. In some cases, a scoring system may be used to assess the likelihood of DIC.

How is disseminated intravascular coagulation (DIC) treated and managed?

The treatment and management of disseminated intravascular coagulation (DIC) are aimed at addressing the underlying cause and preventing further clotting and bleeding. The specific treatment approach will vary depending on the severity of the condition and the underlying cause.

• Treatment of the underlying cause: The most important step in the treatment of DIC is to identify and address the underlying cause. This may involve treating an infection, removing a tumor, or controlling bleeding.
• Replacement of clotting factors and platelets: If clotting factors or platelets are consumed, they may need to be replaced. This can be done with transfusions of fresh frozen plasma, cryoprecipitate, or platelets.
• Anticoagulation therapy: Anticoagulation therapy can be used to prevent further clotting. This may involve the use of heparin, warfarin, or other anticoagulant medications.
• Fibrinolytic therapy: Fibrinolytic therapy can be used to break down blood clots. This may involve the use of alteplase, streptokinase, or other fibrinolytic medications.

In addition to these specific treatments, supportive care is also important. This may include:

• Fluid resuscitation: Fluid resuscitation may be necessary to maintain blood volume and blood pressure.
• Organ support: Organ support may be necessary if DIC has caused damage to organs such as the kidneys, liver, or lungs.
• Nutritional support: Nutritional support may be necessary to ensure that the body is getting the nutrients it needs to heal.

The prognosis of DIC depends on the severity of the condition and the underlying cause. With early diagnosis and appropriate treatment, the outcome can be improved. However, DIC is a serious condition with a high mortality rate.

Key Points of DIC

Definition

Widespread activation of coagulation and fibrinolytic pathways as a secondary complication causing generalized haemorrhage and thrombosis

Causes

• Hypersensitivity reactions
  • Incompatible transfusion reaction
  • Incompatible organ transplantation
• Infections
  • Gram-negative and meningococcal sepsis
  • Severe malaria
  • Viral infections
• Neoplasms
  • Acute promyelocytic leukemia
  • Adenocarcinoma

• Obstetric complications
  • Abruptio placentae
  • Amniotic fluid embolism
  • Eclampsia & toxemia
  • Retained fetus / placenta
  • Septic abortion
• Vascular disorders
  • Aortic aneurysm
  • Cardiac bypass surgery
  • Giant hemangioma

• Widespread tissue injury
  • Burns
  • Surgery
  • Trauma
• Miscellaneous
  • Heat stroke
  • Hypothermia
  • Liver failure
  • Pancreatitis
  • Shock
  • Snake bites

Pathophysiology of DIC

Clinical features

• Bleeding
• Thrombosis
• Tissue damage and necrosis due to thrombosis

Laboratory investigations

Peripheral blood characteristics

Microangiopathic hemolytic anemia, thrombocytopenia

Other important investigations and expected results

• ↑: APTT, PT, TT, bleeding time, FDP, D-dimer
• ↓: platelet count, fibrinogen

Treatment and management

• Treat the underlying cause
• Bleeding: supportive therapy with fresh frozen plasma, platelet concentrates and cryoprecipitate
• Thrombosis: anticoagulant therapy i.e. heparin
• Protein C concentrate and antithrombin in selected patients

References

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