Protein C in the treatment of coagulopathy in meningococcal disease

Rintala, Esa; Seppälä, Olli-Pekka; Kotilainen, Pirkko; Pettilä, Ville; Rasi, Vesa

doi:10.1097/00003246-199805000-00038

Cited by 95 publications

(48 citation statements)

References 16 publications

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“…In one particular study, patients with a poor prognosis responded well to Ceprotin therapy [4,5]. In that similar study, no haemorrhage or thrombotic events were noted after the initiation of Ceprotin therapy [5]. Hence, we strongly urge the need for a standardized protocol in further studies on the treatment with Ceprotin in sepsis-induced coagulopathy.…”

Section: Case Reportmentioning

confidence: 98%

“…In addition to arterial vasoconstriction there is likely some component of thrombosis in the microvessels that leads to this condition [3,4]. Some studies have shown intravenous vasodilators such as nitroglycerin and nitroprusside to be beneficial [4,5]. In severe cases, amputation of the gangrenous limb is the last resort.…”

Section: Case Reportmentioning

confidence: 99%

“…In severe cases, amputation of the gangrenous limb is the last resort. However, few studies have shown that Ceprotin seems to be an effective and therapeutic option in patients with DIC and purpura fulminans [5]. In one particular study, patients with a poor prognosis responded well to Ceprotin therapy [4,5].…”

Section: Case Reportmentioning

confidence: 99%

“…However, few studies have shown that Ceprotin seems to be an effective and therapeutic option in patients with DIC and purpura fulminans [5]. In one particular study, patients with a poor prognosis responded well to Ceprotin therapy [4,5]. In that similar study, no haemorrhage or thrombotic events were noted after the initiation of Ceprotin therapy [5].…”

Section: Case Reportmentioning

confidence: 99%

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A Case of Diffuse Ischemic Limb Gangrene with Palpable Pulses in a Patient with Septic Shock

Gill¹,

Mann²,

Kaur³

et al. 2017

Arch Med

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It is widely believed that ischemic limb gangrene is sequelae of arterial thrombosis or thromboembolism. In patients with severe sepsis, there is widespread activation of acute systemic inflammatory response. This can activate the coagulation cascade in the smaller vessels, therefore the pulse may still be palpable but patients may have ischemic injury due to vasoconstriction. Sepsis is also known to be associated with disseminated intravascular coagulation (DIC) because of hypercoagulable state and subsequent consumption of platelets and coagulation proteins.

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Section: Case Reportmentioning

confidence: 98%

Section: Case Reportmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

See 2 more Smart Citations

A Case of Diffuse Ischemic Limb Gangrene with Palpable Pulses in a Patient with Septic Shock

Gill¹,

Mann²,

Kaur³

et al. 2017

Arch Med

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“…Protein C is a candidate for treatment of certain thrombotic states. 24,25 Moreover, APC has recently been shown to be efficient in the treatment of sepsis, a life-threatening condition associated with hypercoagulation and generalized inflammatory reactions. 26 APC not only has anticoagulant properties but also anti-inflammatory effects, which are poorly understood.…”

mentioning

confidence: 99%

Gla domain–mutated human protein C exhibiting enhanced anticoagulant activity and increased phospholipid binding

Sun

Shen

Dahlbäck

2003

Blood

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Protein C is a member of the vitamin Kdependent protein family. Proteins in this family have similar ␥-carboxyglutamic acid (Gla)-rich domains, but their affinities for negatively charged phospholipid membranes vary more than 1000-fold. We have shown that it is possible to enhance anticoagulant activity and membrane affinity of protein C by selective mutagenesis of the Gla domain. In this study, 3 new mutants, Q10G11N12 ( IntroductionNegatively charged phospholipid membranes play an important role in blood coagulation, providing a suitable surface for the assembly of enzyme-cofactor complexes, which efficiently convert circulating zymogens to active enzymes. Phosphatidylserine (PS) is a key component in the negatively charged membrane that supports the clotting reactions. [1][2][3] In most cells, PS is normally mainly present in the inner leaflet of the cell membrane, but certain cellular processes such as platelet activation result in the exposure of PS on the cell surface. The vitamin K-dependent coagulation proteins in plasma bind to the surface of negatively charged phospholipid with a common mechanism involving the ␥-carboxyglutamic acid (Gla)-rich domains of these proteins. 4 Vitamin K is required in the posttranslational carboxylation of glutamic acid residues to Gla. 5 The Gla domains comprise approximately 45 amino acid residues, and they are structurally very similar in the different vitamin K-dependent proteins. 6 Despite the extensive structural similarity between different Gla domains, they bind negatively charged phospholipid with very different affinity, with dissociation constants (K d 's) ranging more than 1000-fold. 6 This variation in phospholipid binding ability is related to amino acid sequence differences at relatively few positions. This has made it possible to modulate the phospholipid binding abilities of this group of proteins by site-directed mutagenesis. [7][8][9] The nonvitamin K-dependent cofactors of blood coagulation also interact with the phospholipid membranes, certain proteins being membrane spanning, whereas others, such as factor V (FV) and factor VIII (FVIII), contain binding sites for negatively charged phospholipid membranes. 2,10 FV circulates as a procofactor to activated FV (FVa), which functions as a cofactor to activated FX (FXa) in the activation of prothrombin to thrombin. Activated FVIII (FVIIIa) serves a similar function in the FIXa-mediated activation of FX. 2,3 The protein C anticoagulant system, which includes the vitamin K-dependent proteins protein C and protein S, regulates the activities of FVa and FVIIIa by limited proteolysis (reviewed by Dahlbäck et al 11 and Esmon et al 12 ). Protein C is activated on the endothelial cell surface by the thrombin-thrombomodulin complex, and the serine protease activated protein C (APC) down-regulates coagulation by cleaving a limited number of peptide bonds in each of FVa and FVIIIa. Protein S serves as a cofactor to APC by increasing the affinity of APC for the membrane 13 and also by changing the distance of the activ...

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Veränderungen der Hämostase bei Sepsis: disseminierte intravasale Gerinnung, Verbrauchskoagulopathie und sepsisassoziierte Purpura fulminans

Dempfle

Sepsis Und MODS

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Protein C in the treatment of coagulopathy in meningococcal disease

Cited by 95 publications

References 16 publications

A Case of Diffuse Ischemic Limb Gangrene with Palpable Pulses in a Patient with Septic Shock

A Case of Diffuse Ischemic Limb Gangrene with Palpable Pulses in a Patient with Septic Shock

Gla domain–mutated human protein C exhibiting enhanced anticoagulant activity and increased phospholipid binding

Veränderungen der Hämostase bei Sepsis: disseminierte intravasale Gerinnung, Verbrauchskoagulopathie und sepsisassoziierte Purpura fulminans

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