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WILLIAM'S HEMATOLOGY > 127 Disseminated Intravascular Coagulation > Flashcards

127 Disseminated Intravascular Coagulation Flashcards

1
Q

The organs most frequently involved by diffuse microthrombi

A

Lungs and kidneys

Followed by the brain, heart, liver, spleen, adrenal glands, pancreas, and gut

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2
Q

The most important mediators responsible for the imbalance in DIC

A

Cytokines

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3
Q

The most important interface in which the interaction between inflammation and coagulation takes place

A

Endothelium of the capillary bed

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4
Q

Constitutes a sine qua non for most patients with DIC

A

Endothelial perturbation

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5
Q

Plays a central role in the initiation of inflammation-induced coagulation in DIC

A

Tissue factor (TF)

TF becomes exposed to blood upon disruption of the vascular integrity, or when cells present in the circulation, such as monocytes, are triggered to express TF.

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6
Q

The in vivo expression of TF is dependent on what cytokine

A

Interleukin (IL)-6

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7
Q

Other cytokines generated during inflammation, impair the physiologic anticoagulant pathways.

A

Tumor necrosis factor (TNF)-α and IL-1

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8
Q

Thrombin generated by the TF pathway amplifies both clotting and inflammation through the following activities:

A
  • (a) it activates platelets, giving rise to platelet aggregation and augmenting platelet functions in coagulation;
  • (b) it activates factors VIII, V, and XI, yielding further thrombin generation;
  • (c) it activates proinflammatory factors via protease-activated receptors (PARs) on inflammatory cells;
  • (d) it activates factor XIII to factor XIIIa, which crosslinks fibrin clots;
  • (e) it activates thrombin-activatable fibrinolysis inhibitor (TAFI), making clots resistant to fibrinolysis; and
  • (f) it increases expression of adhesion molecules, such as L-selectin, thereby promoting the inflammatory effects of leukocytes

Paradoxically, at low concentrations, thrombin exhibits both antiinflammatory and anticoagulant effects because it binds to thrombomodulin and activates protein C to the activated form, which, in turn, downregulates inflammation and serves as an “off switch” for further thrombin generation

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9
Q

The effects of fibrinogen on mononuclear cells seem to be mediated by

A

Toll-like receptor–4

It is also the receptor of endotoxin.

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10
Q

Procoagulant activity is regulated by three important anticoagulant pathways:

A

AT, the protein C system, and TFPI

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11
Q

Main inhibitor of thrombin and factor Xa

A

AT

  • Without heparin, AT neutralizes coagulation enzymes in a slow, progressive manner.
  • Heparin induces conformational changes in AT that result in at least a 1000-fold enhancement of AT activity.
  • Thus, the clinical efficacy of heparin is attributed to its interaction with AT.
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12
Q

Acts with its cofactor protein S and degrades the essential cofactors Va and VIIIa, and hence, is an effective anticoagulant

A

APC

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13
Q

The main inhibitor of the TF–factor VIIa complex and factor Xa

A

TFPI

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14
Q

ROLE OF NATURAL ANTICOAGULANT PATHWAYS

(Increased or Decreased)

AT:
Glycosaminoglycans:
Zymogen protein C:
Thrombomodulin:
Plasma levels of C4bBP:
EPCR:
Factor VIII:

A

AT: decrease
Glycosaminoglycans:decrease
Zymogen protein C: decrease
Thrombomodulin: decrease
Plasma levels of C4bBP: increase
EPCR: decrease
Factor VIII: increase

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15
Q

Inhibits platelet activation and aggregation, blocks neutrophil tethering to blood vessels, and decreases endothelial cell production of various cytokines and chemokines

A

Prostacyclin

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16
Q

TRUE OR FALSE

LPS-induced DIC so prominently displays tissue infarction leading to multiorgan dysfunction (eg, sepsis) compared with DIC that is predominately induced by TF exposure (eg, head trauma)

A

TRUE

LPS-induced DIC so prominently displays tissue infarction leading to multiorgan dysfunction (eg, sepsis) compared with DIC that is predominately induced by TF exposure (eg, head trauma)

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17
Q

TRUE OR FALSE

The occurrence of schistocytes in the blood film is uncommon in patients with DIC

A

FALSE

The occurrence of schistocytes in the blood film is not uncommon in patients with DIC

Patients with DIC may also display signs of thrombotic microangiopathy, causing further consumption of platelets, and nonimmune hemolysis.

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18
Q

A crucial factor in the pathogenesis of this enhanced platelet–vessel wall interaction is

A

Release of (ultra-large) von Willebrand factor multimers

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19
Q

Account for approximately two-thirds of DIC cases in the major series

A

Infectious diseases and malignant disorders

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20
Q

TRUE OR FALSE

Patients with chronic DIC usually exhibit major skin and mucosal bleeding.

A

TRUE

Patients with chronic DIC usually exhibit only minor skin and mucosal bleeding.

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21
Q

The major causes of renal dysfunction in DIC

A

Renal cortical ischemia induced by microthrombosis of afferent glomerular arterioles and acute tubular necrosis related to hypotension

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22
Q

TRUE OR FALSE

No single laboratory test is sensitive or specific enough to allow a definite diagnosis of DIC

A

TRUE

No single laboratory test is sensitive or specific enough to allow a definite diagnosis of DIC

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23
Q

One of the best parameters for detection of ongoing DIC

A

Soluble fibrin in plasma

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24
Q

Conditions associated with elevated FDPs

A

Trauma, recent surgery, inflammation, or venous thromboembolism

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25
Q

Marker that is elevated in patients with DIC, but this poorly distinguishes patients with DIC from patients with venous thromboembolism, recent surgery, or inflammatory conditions.

A

D-dimer

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26
Q

International Society on Thrombosis and Haemostasis (ISTH) score indicative of DIC

A

5 or more

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27
Q

ISTH Score

A
  • Presence of an underlying disorder known to be associated with DIC
  • Platelet count (>100 = 0; <100 = 1; <50 = 2)
  • Level of fibrin markers (soluble fibrin monomers/ fibrin degradation products) (no increase: 0; moderate increase: 2; strong increase: 3)
  • Prolonged prothrombin time (<3 s = 0; >3 s but <6 s = 1; >6 s = 2)
  • Fibrinogen level (>1.0 g/L = 0; <1.0 g/L = 1)
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28
Q

Test that has advantage of providing an idea of platelet function as well as fibrinolytic activity

A

Thromboelastography (TEG)

29
Q

The most common causes of DIC

A

Bacterial infections

Clinically overt DIC may occur in 30% to 50% of patients with gram-negative sepsis.

30
Q

Characterized by deep tissue infection, vascular collapse, vascular leakage, and multiorgan dysfunction

A

Group A Streptococcus toxic shock syndrome

A streptococcal M protein forms complexes with fibrinogen, and these complexes bind to β2 integrins of neutrophils leading to their activatio

31
Q

A fulminant gram-negative infection characterized by extensive hemorrhagic necrosis, DIC, and shock

A

Meningococcemia

More frequent gram-negative infections associated with DIC are caused by Pseudomonas aeruginosa, E coli, and Proteus vulgaris.

32
Q

Occurs in patients with sepsis-induced DIC and is associated with a high incidence of acute renal failure

A

Severe secondary deficiency of a disintegrin-like metalloprotease with thrombospondin type 1 repeats (ADAMTS13)

33
Q

Can cause DIC accompanied by renal cortical and dermal necrosis.

A

Staphylococcus aureus bacteremia

Related to an α-toxin that activates platelets and induces IL-1 secretion by macrophages

34
Q

Syndrome in asplenic patients with streptococcus pneumoniae and meningococcal infections

A

Waterhouse-Friderichsen syndrome

35
Q

Has been reported in patients with infections and either hereditary thrombophilias or acquired antibodies to protein S

A

Purpura fulminans associated with DIC

36
Q

The most striking coagulation test abnormality in severe COVID-19 patients

A

Abnormally high D-dimer level

Patients with D-dimer levels more than sixfold the upper limit of normal were found to have an increased need for mechanical ventilation and a significantly higher risk of death.

The clinical presentation of the COVID-19 coagulopathy is mostly prothrombotic with a high incidence of overt venous (and possibly arterial) thromboembolism

37
Q

TRUE OR FALSE

COVID 19 is associated with severe thrombocytopenia.

A

FALSE

COVID 19 is associated with mild thrombocytopenia.

Most patients with COVID-19 have a platelet count between 100 and 150 x 109/L; lower platelet counts are rarely (<5%) seen.

A low platelet count in COVID-19 has not been associated with an adverse outcome (although very low platelet counts can be an exception)

38
Q

All patients with COVID-19 that are admitted to the hospital should receive ___________ prophylaxis

A

Heparin

39
Q

A severe, often lethal form of DIC in which extensive areas of the skin over the extremities and buttocks undergo hemorrhagic necrosis.

A

Purpura fulminans

  • Affects infants and children predominantly and occasionally adults.
  • Onset can be within 2 to 4 weeks of a mild infection such as scarlet fever, varicella, or rubella, or can occur during an acute viral or bacterial infection in patients with acquired or hereditary thrombophilias affecting the protein C inhibitory pathway.
  • Are acutely ill with fever, hypotension, and hemorrhage from multiple sites; they frequently have typical laboratory signs of DIC
40
Q

TRUE OR FALSE

Patients with solid tumors and DIC are more prone to thrombosis than to bleeding, whereas patients with leukemia and DIC are more prone to hemorrhage.

A

TRUE

Patients with solid tumors and DIC are more prone to thrombosis than to bleeding, whereas patients with leukemia and DIC are more prone to hemorrhage.

41
Q

Identified as one of the most important proinflammatory cytokines that is able to induce TF expression on cells.

A

IL-6

42
Q

Changes in fibrinolysis and microvascular physiologic anticoagulant pathways are mostly dependent on

A

TNF-α

Other cytokines that participate in the systemic activation of coagulation are IL-1β and IL-8, whereas antiinflammatory cytokines, such as IL-10, are able to inhibit DIC.

43
Q

Microangiopathic hemolytic anemia frequently is induced by DIC in patients with malignancies and is particularly severe in patients with widespread intravascular metastases of

A

Mucin-secreting adenocarcinomas

44
Q

Type of leukemia in which DIC is present in more than 90% of patients at the time of diagnosis or after initiation of remission induction.

A

Acute promyelocytic leukemia (APL)

All-transretinoic acid may induce thrombotic complications as it stimulates blasts to differentiate, whereby they can release prohemostatic triggers.

45
Q

The the most immediate triggers of DIC in trauma

A

Extensive exposure of TF to the blood circulation and hemorrhagic shock

46
Q

A syndrome characterized by a rise in body temperature to higher than 42 C, which follows collapse of the thermoregulatory mechanism

A

Heat stroke

47
Q

Treatment of choice for hemangioma

A

Glucocorticoids

48
Q

Treatment of choice for hemangioma in life-threatening circumstances after failure of glucocorticoid therapy

A

Radiotherapy and interferon-α

49
Q

Pregnancy predisposes patients to DIC for at least four reasons:

A
  1. Pregnancy itself produces a hypercoagulable state, manifested by evidence of lowgrade thrombin generation, with elevated levels of fibrin monomer complexes and fibrinopeptide A
  2. During labor, leakage of TF from placental tissue into the maternal circulation causes a hypercoagulable state
  3. Pregnancy is associated with reduced fibrinolytic activity because of increased plasma levels of PAI-1; and
  4. Pregnancy is associated with a decline in the plasma level of protein S

DIC may be difficult to diagnose during pregnancy because of the high initial levels of coagulation factors such as fibrinogen, factor VIII, and factor VII.

Thrombocytopenia may be particularly helpful in determining whether DIC is present, provided other causes of thrombocytopenia are excluded.

50
Q

Treatment of choice for placental abruption

A

Rapid volume replenishment and evacuation of the uterus

Transfusion of cryoprecipitate, fresh-frozen plasma, and platelets should be given when profuse bleeding occurs.

However, in the absence of severe bleeding, administration of blood components may not be necessary because depleted coagulation factors increase rapidly after delivery.

51
Q

TRUE OR FALSE

Patients predisposed to amniotic fluid embolism are multiparous women whose pregnancies are postmature with large fetuses and women undergoing a tumultuous labor after pharmacologic or surgical induction.

A

TRUE

Patients predisposed to amniotic fluid embolism are multiparous women whose pregnancies are postmature with large fetuses and women undergoing a tumultuous labor after pharmacologic or surgical induction.

52
Q

TRUE OR FALSE

HELLP syndrome occurs more often in whites, multiparous women, and women older than 35 years.

A

TRUE

HELLP syndrome occurs more often in whites, multiparous women, and women older than 35 years.

53
Q

Organisms that are common causes of sepsis during pregnancy

A

Gram-negative bacteria, group A streptococci, and Clostridium perfringens

54
Q

Acute fatty liver of pregnancy is a rare disorder that occurs during the

A

Third trimester of pregnancy

55
Q

In 15% to 20% of cases, acute fatty liver of pregnancy is associated with fetal homozygosity or compound heterozygosity for _______________ deficiency.

A

Long-chain acyl-coenzyme A dehydrogenase (LCAD) deficiency

Infants born with LCAD deficiency fail to thrive and are prone to liver failure and death.

LCAD is one of four enzymes taking part in β-oxidation of fatty acids in mitochondria.

55
Q

Characterized by severe liver dysfunction, renal failure, hypertension, and signs of DIC

A

Acute fatty liver of pregnancy

The typical histologic feature is microvesicular fatty infiltration of the liver.

56
Q

Newborns have a limited capacity to cope with triggers of DIC for several reasons:

A
  • (a) their ability to clear soluble fibrin and activated factors is reduced;
  • (b) their fibrinolytic potential is decreased because of a low plasminogen level; and
  • their capacity to synthesize coagulation factors and inhibitors is limited

Criteria for diagnosis of DIC in newborns are different from those for diagnosis in adults.

57
Q

Physiologic hemostatic findings common in newborns

A
  • Low levels of the vitamin K–dependent factors,
  • Reduced AT and protein C levels
  • Prolonged thrombin time
58
Q

The most common manifestation of DIC in newborns

A

Bleeding from multiple sites

59
Q

Most life-threatening condition in newborns

A

Intracranial hemorrhage

60
Q

TRUE OR FALSE

The survival of patients with DIC depends on vigorous treatment of the underlying disorder to alleviate or remove the inciting injurious cause.

A

TRUE

The survival of patients with DIC depends on vigorous treatment of the underlying disorder to alleviate or remove the inciting injurious cause.

61
Q

Plasma or platelet substitution therapy should not be instituted on the basis of laboratory results alone; it is indicated only in patients with

A

Active bleeding and in those requiring an invasive procedure or who are at risk for bleeding complications

Coagulation factor concentrates, such as prothrombin complex concentrate, may partially overcome this obstacle but do not contain essential factors, such as factor V.

62
Q

Cryoprecipitate can be used to rapidly raise the fibrinogen and factor VIII levels, particularly when bleeding is part of the DIC and fibrinogen level is less than ___ g/L.

A

Less than 1 g/L

Cryoprecipitate has at least four to five times the mass of fibrinogen per milliliter of infusate compared with fresh-frozen plasma.

Fresh-frozen plasma contains fibrinogen in sufficient amounts for treatment of patients with mild to moderate hypofibrinogemia.

63
Q

Replacement therapy for thrombocytopenia should consist of 5 to 10 units of platelet concentrate or single-donor apheresis-derived platelets to raise the platelet count to 20–30 x109/L and, in patients who need an invasive procedure, to ________ x 109/L.

A

50 x 109/L

64
Q

TRUE OR FALSE

Administration of heparin is beneficial in some categories of acute DIC

A

FALSE

Administration of heparin is beneficial in some categories of chronic DIC

Such as metastatic carcinomas, purpura fulminans, and aortic aneurysm (before resection)

Heparin also is indicated for treating thromboembolic complications in large vessels and before surgery in patients with chronic DIC

In acute DIC when intensive blood component replacement fails to improve excessive bleeding or when thrombosis threatens to cause irreversible tissue injury (eg, acute cortical necrosis of the kidney or digital gangrene).

65
Q

Theoretically, the most logical anticoagulant agent to use in DIC is directed against

A

TF

Potential agents include recombinant TFPI, inactivated factor VIIa, and recombinant nematode anticoagulant protein c2 (NAPc2), a potent and specific inhibitor of the ternary complex of TF–factor VIIa and factor Xa.

66
Q

TRUE OR FALSE

Patients with DIC must be treated with antifibrinolytic agents such as ε-aminocaproic acid or tranexamic acid.

A

FALSE

Patients with DIC should not be treated with antifibrinolytic agents such as ε-aminocaproic acid or tranexamic acid.

Because these drugs block fibrinolysis that preserves tissue perfusion in patients with DIC

67
Q

Conditions wherein the use of fibrinolytic inhibitors can be considered

A

DIC accompanied by primary fibrino(geno)lysis, as in some cases of APL, giant hemangioma, heat stroke, amniotic fluid embolism, some forms of liver disease, and metastatic carcinoma of the prostate

Provided:
* (a) the patient is bleeding profusely and has not responded to replacement therapy and
* (b) excessive fibrino(geno)lysis is observed, ie, rapid whole blood clot lysis or a very short euglobulin lysis time.

In such circumstances, use of antifibrinolytic agents should be preceded by replacement of depleted blood components and continuous heparin infusion

WILLIAM'S HEMATOLOGY (91 decks)

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