Subscribe to RSS
DOI: 10.1055/s-0031-1297375
Microvascular Thrombosis: A Serious and Deadly Pathologic Process in Multiple Diseases
Publication History
Publication Date:
23 December 2011 (online)

ABSTRACT
Much of our understanding of the pathogenesis of thrombosis has long been based on observations made on large blood vessels. Nevertheless, there has been a recent shift in our attention to the microvasculature and to how microcirculatory occlusion affects function of various organs in diseases. This article provides an overview of microthrombosis in small blood vessels, with discussion of the progressive stages of its development. The initial event is triggered by a variety of diseases, followed by a second phase when multiple contributory factors amplify the process with the final phase of microvascular occlusion and microvascular thrombosis. The outcome is either recovery or injury to the affected organ. If the process is generalized, it is often associated with catastrophic or fatal outcomes. Our current knowledge of the major role of contributory factors leads to a new paradigm. A therapeutic approach limited to a single target of the underlying pathogenic factor, such as the use of anticoagulants, is insufficient and too often unsuccessful. Simultaneous management of all the contributory factors should therefore be considered.
KEYWORDS
Thrombosis - disseminated intravascular coagulation - inflammation - hypercoagulable state - sepsis
REFERENCES
- 1
Aird W C.
Spatial and temporal dynamics of the endothelium.
J Thromb Haemost.
2005;
3
(7)
1392-1406
MissingFormLabel
- 2
Lipowsky H H.
Microvascular rheology and hemodynamics.
Microcirculation.
2005;
12
(1)
5-15
MissingFormLabel
- 3
Baskurt O K, Meiselman H J.
Blood rheology and hemodynamics.
Semin Thromb Hemost.
2003;
29
(5)
435-450
MissingFormLabel
- 4
Aird W C.
Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms.
Circ Res.
2007;
100
(2)
158-173
MissingFormLabel
- 5
Aird W C.
Phenotypic heterogeneity of the endothelium: II. Representative vascular beds.
Circ Res.
2007;
100
(2)
174-190
MissingFormLabel
- 6
Pries A R, Kuebler W M.
Normal endothelium.
Handb Exp Pharmacol.
2006;
176
(176 Pt 1)
1-40
MissingFormLabel
- 7
Kwaan H C, Samama M M.
The significance of endothelial heterogeneity in thrombosis and hemostasis.
Semin Thromb Hemost.
2010;
36
(3)
286-300
MissingFormLabel
- 8
Ishii H, Salem H H, Bell C E, Laposata E A, Majerus P W.
Thrombomodulin, an endothelial anticoagulant protein, is absent from the human brain.
Blood.
1986;
67
(2)
362-365
MissingFormLabel
- 9
Esmon C T, Gu J M, Xu J, Qu D, Stearns-Kurosawa D J, Kurosawa S.
Regulation and functions of the protein C anticoagulant pathway.
Haematologica.
1999;
84
(4)
363-368
MissingFormLabel
- 10
Lippi G, Franchini M.
Pathogenesis of venous thromboembolism: when the cup runneth over.
Semin Thromb Hemost.
2008;
34
(8)
747-761
MissingFormLabel
- 11
Lippi G, Franchini M, Favaloro E J.
Unsuspected triggers of venous thromboembolism—trivial or not so trivial?.
Semin Thromb Hemost.
2009;
35
(7)
597-604
MissingFormLabel
- 12 Virchow R. Phlogose und Thrombose in Gefabsystem. In: Gesammelte Abhandlungen zur Wissenschaftlichen Medizin. Frankfurt, Germany: Von Meidinger Sohn; 1856: 458
MissingFormLabel
- 13
Levi M, Schultz M, van der Poll T.
Disseminated intravascular coagulation in infectious disease.
Semin Thromb Hemost.
2010;
36
(4)
367-377
MissingFormLabel
- 14
Galindo M, Gonzalo E, Martinez-Vidal M P et al..
Immunohistochemical detection of intravascular platelet microthrombi in patients with
lupus nephritis and anti-phospholipid antibodies.
Rheumatology (Oxford).
2009;
48
(8)
1003-1007
MissingFormLabel
- 15
Nagy J A, Chang S H, Shih S C, Dvorak A M, Dvorak H F.
Heterogeneity of the tumor vasculature.
Semin Thromb Hemost.
2010;
36
(3)
321-331
MissingFormLabel
- 16
Rubin D B, Drab E A, Ward W F.
Physiological and biochemical markers of the endothelial cell response to irradiation.
Int J Radiat Biol.
1991;
60
(1-2)
29-32
MissingFormLabel
- 17
Kloner R A, Ganote C E, Jennings R B.
The “no-reflow” phenomenon after temporary coronary occlusion in the dog.
J Clin Invest.
1974;
54
(6)
1496-1508
MissingFormLabel
- 18
Brands M T, van den Bosch S C, Dieleman F J, Bergé S J, Merkx M A.
Prevention of thrombosis after microvascular tissue transfer in the head and neck.
A review of the literature and the state of affairs in Dutch Head and Neck Cancer
Centers.
Int J Oral Maxillofac Surg.
2010;
39
(2)
101-106
MissingFormLabel
- 19
Lecoq J P, Senard M, Hartstein G M, Lamy M, Heymans O.
Thromboprophylaxis in microsurgery.
Acta Chir Belg.
2006;
106
(2)
158-164
MissingFormLabel
- 20
Kwaan H C, Bongu A.
The hyperviscosity syndromes.
Semin Thromb Hemost.
1999;
25
(2)
199-208
MissingFormLabel
- 21
Esmon C T.
The impact of the inflammatory response on coagulation.
Thromb Res.
2004;
114
(5-6)
321-327
MissingFormLabel
- 22
Esmon C T.
The interactions between inflammation and coagulation.
Br J Haematol.
2005;
131
(4)
417-430
MissingFormLabel
- 23
Levi M.
The coagulant response in sepsis and inflammation.
Hamostaseologie.
2010;
30
(1)
10-12, 14–16
MissingFormLabel
- 24
Bevilacqua M P, Pober J S, Majeau G R, Fiers W, Cotran R S, Gimbrone Jr M A.
Recombinant tumor necrosis factor induces procoagulant activity in cultured human
vascular endothelium: characterization and comparison with the actions of interleukin
1.
Proc Natl Acad Sci U S A.
1986;
83
(12)
4533-4537
MissingFormLabel
- 25
Coughlin S R.
Thrombin signalling and protease-activated receptors.
Nature.
2000;
407
(6801)
258-264
MissingFormLabel
- 26
Bevilacqua M P, Nelson R M.
Endothelial-leukocyte adhesion molecules in inflammation and metastasis.
Thromb Haemost.
1993;
70
(1)
152-154
MissingFormLabel
- 27
Gando S.
Microvascular thrombosis and multiple organ dysfunction syndrome.
Crit Care Med.
2010;
38
(2, Suppl)
S35-S42
MissingFormLabel
- 28
Lee C C, Marill K A, Carter W A, Crupi R S.
A current concept of trauma-induced multiorgan failure.
Ann Emerg Med.
2001;
38
(2)
170-176
MissingFormLabel
- 29
Hertig A, Rondeau E.
Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury.
J Am Soc Nephrol.
2004;
15
(4)
844-853
MissingFormLabel
- 30
Welty-Wolf K E, Carraway M S, Ortel T L, Piantadosi C A.
Coagulation and inflammation in acute lung injury.
Thromb Haemost.
2002;
88
(1)
17-25
MissingFormLabel
- 31
Dhainaut J F, Marin N, Mignon A, Vinsonneau C.
Hepatic response to sepsis: interaction between coagulation and inflammatory processes.
Crit Care Med.
2001;
29
(7, Suppl)
S42-S47
MissingFormLabel
- 32
Papadopoulos M C, Davies D C, Moss R F, Tighe D, Bennett E D.
Pathophysiology of septic encephalopathy: a review.
Crit Care Med.
2000;
28
(8)
3019-3024
MissingFormLabel
- 33
Stegmayr B G.
Apheresis as therapy for patients with severe sepsis and multiorgan dysfunction syndrome.
Ther Apher.
2001;
5
(2)
123-127
MissingFormLabel
- 34
Levi M, Ten Cate H.
Disseminated intravascular coagulation.
N Engl J Med.
1999;
341
(8)
586-592
MissingFormLabel
- 35
ten Cate H, Timmerman J J, Levi M.
The pathophysiology of disseminated intravascular coagulation.
Thromb Haemost.
1999;
82
(2)
713-717
MissingFormLabel
- 36
Lippi G, Cervellin G.
Disseminated intravascular coagulation in trauma injuries.
Semin Thromb Hemost.
2010;
36
(4)
378-387
MissingFormLabel
- 37
Kojima M, Shimamura K, Mori N, Oka K, Nakazawa M.
A histological study on microthrombi in autopsy cases of DIC.
Bibl Haematol.
1983;
(49)
95-106
MissingFormLabel
- 38
Shimamura K, Oka K, Nakazawa M, Kojima M.
Distribution patterns of microthrombi in disseminated intravascular coagulation.
Arch Pathol Lab Med.
1983;
107
(10)
543-547
MissingFormLabel
- 39
Schouten M, Wiersinga W J, Levi M, van der Poll T.
Inflammation, endothelium, and coagulation in sepsis.
J Leukoc Biol.
2008;
83
(3)
536-545
MissingFormLabel
- 40
Osterud B.
Tissue factor expression by monocytes: regulation and pathophysiological roles.
Blood Coagul Fibrinolysis.
1998;
9
(Suppl 1)
S9-S14
MissingFormLabel
- 41
Meziani F, Delabranche X, Asfar P, Toti F.
Bench-to-bedside review: circulating microparticles—a new player in sepsis?.
Crit Care.
2010;
14
(5)
236
MissingFormLabel
- 42
Soriano A O, Jy W, Chirinos J A et al..
Levels of endothelial and platelet microparticles and their interactions with leukocytes
negatively correlate with organ dysfunction and predict mortality in severe sepsis.
Crit Care Med.
2005;
33
(11)
2540-2546
MissingFormLabel
- 43
McEver R P.
GMP-140: a receptor for neutrophils and monocytes on activated platelets and endothelium.
J Cell Biochem.
1991;
45
(2)
156-161
MissingFormLabel
- 44
Klintman D, Li X, Thorlacius H.
Important role of P-selectin for leukocyte recruitment, hepatocellular injury, and
apoptosis in endotoxemic mice.
Clin Diagn Lab Immunol.
2004;
11
(1)
56-62
MissingFormLabel
- 45
Ward P A.
Role of the complement in experimental sepsis.
J Leukoc Biol.
2008;
83
(3)
467-470
MissingFormLabel
- 46
Laudes I J, Chu J C, Huber-Lang M et al..
Expression and function of C5a receptor in mouse microvascular endothelial cells.
J Immunol.
2002;
169
(10)
5962-5970
MissingFormLabel
- 47
Esmon C T, Fukudome K, Mather T et al..
Inflammation, sepsis, and coagulation.
Haematologica.
1999;
84
(3)
254-259
MissingFormLabel
- 48
Levi M, Lowenberg E, Meijers J C.
Recombinant anticoagulant factors for adjunctive treatment of sepsis.
Semin Thromb Hemost.
2010;
36
(5)
550-557
MissingFormLabel
- 49
Bernard G R, Vincent J L, Laterre P F Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study
group et al.
Efficacy and safety of recombinant human activated protein C for severe sepsis.
N Engl J Med.
2001;
344
(10)
699-709
MissingFormLabel
- 50
Ely E W, Laterre P F, Angus D C PROWESS Investigators et al.
Drotrecogin alfa (activated) administration across clinically important subgroups
of patients with severe sepsis.
Crit Care Med.
2003;
31
(1)
12-19
MissingFormLabel
- 51
Dhainaut J F, Yan S B, Joyce D E et al..
Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with
or without overt disseminated intravascular coagulation.
J Thromb Haemost.
2004;
2
(11)
1924-1933
MissingFormLabel
- 52
Abraham E, Laterre P F, Garg R Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS)
Study Group et al.
Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.
N Engl J Med.
2005;
353
(13)
1332-1341
MissingFormLabel
- 53
Levi M, Levy M, Williams M D Xigris and Prophylactic HepaRin Evaluation in Severe Sepsis (XPRESS) Study Group et al.
Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa
(activated).
Am J Respir Crit Care Med.
2007;
176
(5)
483-490
MissingFormLabel
- 54
Costa V, Brophy J M.
Drotrecogin alfa (activated) in severe sepsis: a systematic review and new cost-effectiveness
analysis.
BMC Anesthesiol.
2007;
7
5
MissingFormLabel
- 55
Barie P S.
“All in” for a huge pot: the PROWESS-SHOCK trial for refractory septic shock.
Surg Infect (Larchmt).
2007;
8
(5)
491-494
MissingFormLabel
- 56
Barie P S.
Current role of activated protein C therapy for severe sepsis and septic shock.
Curr Infect Dis Rep.
2008;
10
(5)
368-376
MissingFormLabel
- 57
Bernard G R, Margolis B D, Shanies H M Extended Evaluation of Recombinant Human Activated Protein C United States Investigators et al.
Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE
US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in
severe sepsis.
Chest.
2004;
125
(6)
2206-2216
MissingFormLabel
- 58
Leitner J M, Firbas C, Mayr F B, Reiter R A, Steinlechner B, Jilma B.
Recombinant human antithrombin inhibits thrombin formation and interleukin 6 release
in human endotoxemia.
Clin Pharmacol Ther.
2006;
79
(1)
23-34
MissingFormLabel
- 59
Warren B L, Eid A, Singer P KyberSept Trial Study Group et al.
Caring for the critically ill patient. High-dose antithrombin III in severe sepsis:
a randomized controlled trial.
JAMA.
2001;
286
(15)
1869-1878
MissingFormLabel
- 60
Ott I, Miyagi Y, Miyazaki K et al..
Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored
tissue factor pathway inhibitor.
Arterioscler Thromb Vasc Biol.
2000;
20
(3)
874-882
MissingFormLabel
- 61
Brandtzaeg P, Sandset P M, Joø G B, Ovstebø R, Abildgaard U, Kierulf P.
The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic
pathway inhibitor and fibrinopeptide A in systemic meningococcal disease.
Thromb Res.
1989;
55
(4)
459-470
MissingFormLabel
- 62
Abraham E, Reinhart K, Opal S OPTIMIST Trial Study Group et al.
Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in
severe sepsis: a randomized controlled trial.
JAMA.
2003;
290
(2)
238-247
MissingFormLabel
- 63
van der Poll T, Levi M, Büller H R et al..
Fibrinolytic response to tumor necrosis factor in healthy subjects.
J Exp Med.
1991;
174
(3)
729-732
MissingFormLabel
- 64
Carmeliet P, Schoonjans L, Kieckens L et al..
Physiological consequences of loss of plasminogen activator gene function in mice.
Nature.
1994;
368
(6470)
419-424
MissingFormLabel
- 65
Bajzar L, Jain N, Wang P, Walker J B.
Thrombin activatable fibrinolysis inhibitor: not just an inhibitor of fibrinolysis.
Crit Care Med.
2004;
32
(5, Suppl)
S320-S324
MissingFormLabel
- 66
Leung L L, Nishimura T, Myles T.
Regulation of tissue inflammation by thrombin-activatable carboxypeptidase B (or TAFI).
Adv Exp Med Biol.
2008;
632
61-69
MissingFormLabel
- 67
Kwaan H C, Gordon L I.
Thrombotic microangiopathy in the cancer patient.
Acta Haematol.
2001;
106
(1-2)
52-56
MissingFormLabel
- 68
Elliott M A, Letendre L, Gastineau D A, Winters J L, Pruthi R K, Heit J A.
Cancer-associated microangiopathic hemolytic anemia with thrombocytopenia: an important
diagnostic consideration.
Eur J Haematol.
2010;
85
(1)
43-50
MissingFormLabel
- 69
Zakarija A.
Thrombotic microangiopathy syndromes.
Cancer Treat Res.
2009;
148
115-136
MissingFormLabel
- 70
Gordon L I, Kwaan H C.
Cancer- and drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic
syndrome.
Semin Hematol.
1997;
34
(2)
140-147
MissingFormLabel
- 71
Kwaan H C, Boggio L N.
The clinical spectrum of thrombotic thrombocytopenic purpura.
Semin Thromb Hemost.
2005;
31
(6)
673-680
MissingFormLabel
- 72
Karpman D, Sartz L, Johnson S.
Pathophysiology of typical hemolytic uremic syndrome.
Semin Thromb Hemost.
2010;
36
(6)
575-585
MissingFormLabel
- 73
Baronzio G, Freitas I, Kwaan H C.
Tumor microenvironment and hemorheological abnormalities.
Semin Thromb Hemost.
2003;
29
(5)
489-497
MissingFormLabel
- 74
Brat D J, Van Meir E G.
Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis,
and accelerated growth in glioblastoma.
Lab Invest.
2004;
84
(4)
397-405
MissingFormLabel
- 75
Wang J, Weiss I, Svoboda K, Kwaan H C.
Thrombogenic role of cells undergoing apoptosis.
Br J Haematol.
2001;
115
(2)
382-391
MissingFormLabel
- 76
Rak J.
Microparticles in cancer.
Semin Thromb Hemost.
2010;
36
(8)
888-906
MissingFormLabel
- 77
Kwaan H C, Rego E M.
Role of microparticles in the hemostatic dysfunction in acute promyelocytic leukemia.
Semin Thromb Hemost.
2010;
36
(8)
917-924
MissingFormLabel
- 78
Key N S, Kwaan H C.
Microparticles in thrombosis and hemostasis.
Semin Thromb Hemost.
2010;
36
(8)
805-806
MissingFormLabel
- 79
Myhre-Jensen O, Hansen E S, Butrago B.
Renal microthrombosis. Incidence in 500 consecutive autopsies. Clinico-pathological
relations.
Acta Pathol Microbiol Scand [A].
1972;
80
(3)
403-411
MissingFormLabel
- 80
Shih H M, Lin C C, Shiao Y W.
Pulmonary tumor thrombotic microangiopathy.
Am J Emerg Med.
2011;
29
(2)
241, e3-e4
MissingFormLabel
- 81
Chinen K, Tokuda Y, Fujiwara M, Fujioka Y.
Pulmonary tumor thrombotic microangiopathy in patients with gastric carcinoma: an
analysis of 6 autopsy cases and review of the literature.
Pathol Res Pract.
2010;
206
(10)
682-689
MissingFormLabel
- 82
Tehrani M, Friedman T M, Olson J J, Brat D J.
Intravascular thrombosis in central nervous system malignancies: a potential role
in astrocytoma progression to glioblastoma.
Brain Pathol.
2008;
18
(2)
164-171
MissingFormLabel
- 83
Hallahan D, Clark E T, Kuchibhotla J, Gewertz B L, Collins T.
E-selectin gene induction by ionizing radiation is independent of cytokine induction.
Biochem Biophys Res Commun.
1995;
217
(3)
784-795
MissingFormLabel
- 84
Jahroudi N, Ardekani A M, Greenberger J S.
Ionizing irradiation increases transcription of the von Willebrand factor gene in
endothelial cells.
Blood.
1996;
88
(10)
3801-3814
MissingFormLabel
- 85
Verheij M, Dewit L G, van Mourik J A.
The effect of ionizing radiation on endothelial tissue factor activity and its cellular
localization.
Thromb Haemost.
1995;
73
(5)
894-895
MissingFormLabel
- 86
Hauer-Jensen M, Fink L M, Wang J.
Radiation injury and the protein C pathway.
Crit Care Med.
2004;
32
(5, Suppl)
S325-S330
MissingFormLabel
- 87
Astedt B, Bergentz S E, Svanberg L.
Effect of irradiation on the plasminogen activator content in rat vessels.
Experientia.
1974;
30
(12)
1466-1467
MissingFormLabel
- 88
Dropcho E J.
Neurotoxicity of radiation therapy.
Neurol Clin.
2010;
28
(1)
217-234
MissingFormLabel
- 89
Lyons A, Ghazali N.
Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment.
Br J Oral Maxillofac Surg.
2008;
46
(8)
653-660
MissingFormLabel
- 90
Madrid C, Abarca M, Bouferrache K.
Osteoradionecrosis: an update.
Oral Oncol.
2010;
46
(6)
471-474
MissingFormLabel
- 91
Kwaan H C.
Miscellaneous secondary thrombotic microangiopathy.
Semin Hematol.
1987;
24
(3)
141-147
MissingFormLabel
- 92
Kwaan H C.
Thrombotic thrombocytopenic purpura: a diagnostic and therapeutic challenge.
Semin Thromb Hemost.
2005;
31
(6)
615-624
MissingFormLabel
- 93
Mitra D, Jaffe E A, Weksler B, Hajjar K A, Soderland C, Laurence J.
Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas
induce apoptosis in restricted lineages of human microvascular endothelial cells.
Blood.
1997;
89
(4)
1224-1234
MissingFormLabel
- 94
Laurence J, Mitra D.
Apoptosis of microvascular endothelial cells in the pathophysiology of thrombotic
thrombocytopenic purpura/sporadic hemolytic uremic syndrome.
Semin Hematol.
1997;
34
(2)
98-105
MissingFormLabel
- 95
Zipfel P F, Heinen S, Skerka C.
Thrombotic microangiopathies: new insights and new challenges.
Curr Opin Nephrol Hypertens.
2010;
19
(4)
372-378
MissingFormLabel
- 96
Louise C B, Obrig T G.
Shiga toxin-associated hemolytic-uremic syndrome: combined cytotoxic effects of Shiga
toxin, interleukin-1 beta, and tumor necrosis factor alpha on human vascular endothelial
cells in vitro.
Infect Immun.
1991;
59
(11)
4173-4179
MissingFormLabel
- 97
Louise C B, Obrig T G.
Human renal microvascular endothelial cells as a potential target in the development
of the hemolytic uremic syndrome as related to fibrinolysis factor expression, in
vitro.
Microvasc Res.
1994;
47
(3)
377-387
MissingFormLabel
- 98
Dragon-Durey M A, Sethi S K, Bagga A et al..
Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome.
J Am Soc Nephrol.
2010;
21
(12)
2180-2187
MissingFormLabel
- 99
Le Quintrec M, Roumenina L, Noris M, Frémeaux-Bacchi V.
Atypical hemolytic uremic syndrome associated with mutations in complement regulator
genes.
Semin Thromb Hemost.
2010;
36
(6)
641-652
MissingFormLabel
- 100
Heinen S, Hartmann A, Lauer N et al..
Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and
terminal complex formation.
Blood.
2009;
114
(12)
2439-2447
MissingFormLabel
- 101
Kwaan H C.
Miscellaneous secondary thrombotic microangiopathy.
Semin Hematol.
1987;
24
(3)
141-147
MissingFormLabel
- 102
Kelton J G, Warkentin T E.
Heparin-induced thrombocytopenia: a historical perspective.
Blood.
2008;
112
(7)
2607-2616
MissingFormLabel
- 103
Kwaan H C, Sakurai S.
Endothelial cell hyperplasia contributes to thrombosis in heparin-induced thrombocytopenia.
Semin Thromb Hemost.
1999;
25
(Suppl 1)
23-27
MissingFormLabel
- 104
Baskurt O K, Meiselman H J.
Blood rheology and hemodynamics.
Semin Thromb Hemost.
2003;
29
(5)
435-450
MissingFormLabel
- 105
Kwaan H C, Wang J.
Hyperviscosity in polycythemia vera and other red cell abnormalities.
Semin Thromb Hemost.
2003;
29
(5)
451-458
MissingFormLabel
- 106
Newton C R, Marsh K, Peshu N, Kirkham F J.
Perturbations of cerebral hemodynamics in Kenyans with cerebral malaria.
Pediatr Neurol.
1996;
15
(1)
41-49
MissingFormLabel
- 107
Beare N A, Harding S P, Taylor T E, Lewallen S, Molyneux M E.
Perfusion abnormalities in children with cerebral malaria and malarial retinopathy.
J Infect Dis.
2009;
199
(2)
263-271
MissingFormLabel
- 108
Buffet P A, Safeukui I, Deplaine G et al..
The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic
physiology.
Blood.
2011;
117
(2)
381-392
MissingFormLabel
- 109
Grau G E, Mackenzie C D, Carr R A et al..
Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria.
J Infect Dis.
2003;
187
(3)
461-466
MissingFormLabel
- 110
Cox D, McConkey S.
The role of platelets in the pathogenesis of cerebral malaria.
Cell Mol Life Sci.
2010;
67
(4)
557-568
MissingFormLabel
- 111
Baruch D I, Gormely J A, Ma C, Howard R J, Pasloske B L.
Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte
receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule
1.
Proc Natl Acad Sci U S A.
1996;
93
(8)
3497-3502
MissingFormLabel
- 112
Chakravorty S J, Hughes K R, Craig A G.
Host response to cytoadherence in Plasmodium falciparum.
Biochem Soc Trans.
2008;
36
(Pt 2)
221-228
MissingFormLabel
- 113
García F, Cebrián M, Dgedge M et al..
Endothelial cell activation in muscle biopsy samples is related to clinical severity
in human cerebral malaria.
J Infect Dis.
1999;
179
(2)
475-483
MissingFormLabel
- 114
Francischetti I M, Seydel K B, Monteiro R Q et al..
Plasmodium falciparum-infected erythrocytes induce tissue factor expression in endothelial
cells and support the assembly of multimolecular coagulation complexes.
J Thromb Haemost.
2007;
5
(1)
155-165
MissingFormLabel
- 115
Francischetti I M, Seydel K B, Monteiro R Q.
Blood coagulation, inflammation, and malaria.
Microcirculation.
2008;
15
(2)
81-107
MissingFormLabel
- 116
Combes V, Taylor T E, Juhan-Vague I et al..
Circulating endothelial microparticles in malawian children with severe falciparum
malaria complicated with coma.
JAMA.
2004;
291
(21)
2542-2544
MissingFormLabel
- 117
Milner Jr D A.
Rethinking cerebral malaria pathology.
Curr Opin Infect Dis.
2010;
23
(5)
456-463
MissingFormLabel
- 118
Kato G J, Hebbel R P, Steinberg M H, Gladwin M T.
Vasculopathy in sickle cell disease: biology, pathophysiology, genetics, translational
medicine, and new research directions.
Am J Hematol.
2009;
84
(9)
618-625
MissingFormLabel
- 119
Morris C R.
Mechanisms of vasculopathy in sickle cell disease and thalassemia.
Hematology (Am Soc Hematol Educ Program).
2008;
177-185
MissingFormLabel
- 120
Morris C R, Kato G J, Poljakovic M et al..
Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and
mortality in sickle cell disease.
JAMA.
2005;
294
(1)
81-90
MissingFormLabel
- 121
Francis Jr R B.
Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role
in vascular occlusion.
Blood Coagul Fibrinolysis.
1991;
2
(2)
341-353
MissingFormLabel
- 122
Peters M, Plaat B E, ten Cate H, Wolters H J, Weening R S, Brandjes D P.
Enhanced thrombin generation in children with sickle cell disease.
Thromb Haemost.
1994;
71
(2)
169-172
MissingFormLabel
- 123
Key N S, Slungaard A, Dandelet L et al..
Whole blood tissue factor procoagulant activity is elevated in patients with sickle
cell disease.
Blood.
1998;
91
(11)
4216-4223
MissingFormLabel
- 124
Kurantsin-Mills J, Ofosu F A, Safa T K, Siegel R S, Lessin L S.
Plasma factor VII and thrombin-antithrombin III levels indicate increased tissue factor
activity in sickle cell patients.
Br J Haematol.
1992;
81
(4)
539-544
MissingFormLabel
- 125
Nsiri B, Gritli N, Bayoudh F, Messaoud T, Fattoum S, Machghoul S.
Abnormalities of coagulation and fibrinolysis in homozygous sickle cell disease.
Hematol Cell Ther.
1996;
38
(3)
279-284
MissingFormLabel
- 126
Kurantsin-Mills J, Ibe B O, Natta C L, Raj J U, Siegel R S, Lessin L S.
Elevated urinary levels of thromboxane and prostacyclin metabolities in sickle cell
disease reflects activated platelets in the circulation.
Br J Haematol.
1994;
87
(3)
580-585
MissingFormLabel
- 127
Ataga K I, Orringer E P.
Hypercoagulability in sickle cell disease: a curious paradox.
Am J Med.
2003;
115
(9)
721-728
MissingFormLabel
- 128
Gladwin M T, Kato G J.
Hemolysis-associated hypercoagulability in sickle cell disease: the plot (and blood)
thickens!.
Haematologica.
2008;
93
(1)
1-3
MissingFormLabel
- 129
Gladwin M T, Vichinsky E.
Pulmonary complications of sickle cell disease.
N Engl J Med.
2008;
359
(21)
2254-2265
MissingFormLabel
- 130
Bunn H F, Nathan D G, Dover G J et al..
Pulmonary hypertension and nitric oxide depletion in sickle cell disease.
Blood.
2010;
116
(5)
687-692
MissingFormLabel
- 131
Gordeuk V R, Campbell A, Rana S et al..
Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid
regurgitation velocity in children with sickle cell disease.
Blood.
2009;
114
(21)
4639-4644
MissingFormLabel
- 132
Machado R F, Martyr S, Kato G J et al..
Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.
Br J Haematol.
2005;
130
(3)
445-453
MissingFormLabel
- 133
Rose V L, Kwaan H C.
Anti-Pr cold hemagglutination associated with livedo reticularis.
Am J Hematol.
1985;
19
(4)
419-421
MissingFormLabel
- 134
Ruch J, McMahon B, Ramsey G, Kwaan H C.
Catastrophic multiple organ ischemia due to an anti-Pr cold agglutinin developing
in a patient with mixed cryoglobulinemia after treatment with rituximab.
Am J Hematol.
2009;
84
(2)
120-122
MissingFormLabel
- 135
Blum W, Porcu P.
Therapeutic apheresis in hyperleukocytosis and hyperviscosity syndrome.
Semin Thromb Hemost.
2007;
33
(4)
350-354
MissingFormLabel
- 136
Porcu P, Danielson C F, Orazi A, Heerema N A, Gabig T G, McCarthy L J.
Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between
degree of cytoreduction and early mortality rate.
Br J Haematol.
1997;
98
(2)
433-436
MissingFormLabel
- 137
Vaughan W P, Kimball A W, Karp J E, Dragon L H, Burke P J.
Factors affecting survival of patients with acute myelocytic leukemia presenting with
high wbc counts.
Cancer Treat Rep.
1981;
65
(11-12)
1007-1013
MissingFormLabel
- 138
Creutzig U, Ritter J, Budde M, Sutor A, Schellong G.
Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia.
Associations with hyperleukocytosis and acute monocytic leukemia.
Cancer.
1987;
60
(12)
3071-3079
MissingFormLabel
- 139
Cuttner J, Conjalka M S, Reilly M et al..
Association of monocytic leukemia in patients with extreme leukocytosis.
Am J Med.
1980;
69
(4)
555-558
MissingFormLabel
- 140
Scott C S, Stark A N, Limbert H J, Master P S, Head C, Roberts B E.
Diagnostic and prognostic factors in acute monocytic leukaemia: an analysis of 51
cases.
Br J Haematol.
1988;
69
(2)
247-252
MissingFormLabel
- 141
Biondi A, Cimino G, Pieters R, Pui C H.
Biological and therapeutic aspects of infant leukemia.
Blood.
2000;
96
(1)
24-33
MissingFormLabel
- 142
Stucki A, Rivier A S, Gikic M, Monai N, Schapira M, Spertini O.
Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and
leukemic cell dissemination.
Blood.
2001;
97
(7)
2121-2129
MissingFormLabel
- 143
An international randomized trial comparing four thrombolytic strategies for acute
myocardial infarction. The GUSTO investigators.
N Engl J Med.
1993;
329
(10)
673-682
MissingFormLabel
- 144
Beek A M, Nijveldt R, van Rossum A C.
Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous
coronary intervention.
Int J Cardiovasc Imaging.
2010;
26
(1)
49-55
MissingFormLabel
- 145
Patel B, Fisher M.
Therapeutic advances in myocardial microvascular resistance: unravelling the enigma.
Pharmacol Ther.
2010;
127
(2)
131-147
MissingFormLabel
- 146
Bhavsar J, Rosenson R S.
Adenosine transport, erythrocyte deformability and microvascular dysfunction: an unrecognized
potential role for dipyridamole therapy.
Clin Hemorheol Microcirc.
2010;
44
(3)
193-205
MissingFormLabel
- 147
Bekkers S C, Yazdani S K, Virmani R, Waltenberger J.
Microvascular obstruction: underlying pathophysiology and clinical diagnosis.
J Am Coll Cardiol.
2010;
55
(16)
1649-1660
MissingFormLabel
- 148
Buja L M.
Myocardial ischemia and reperfusion injury.
Cardiovasc Pathol.
2005;
14
(4)
170-175
MissingFormLabel
- 149
Khouri R K.
Free flap surgery. The second decade.
Clin Plast Surg.
1992;
19
(4)
757-761
MissingFormLabel
- 150
Ashjian P, Chen C M, Pusic A, Disa J J, Cordeiro P G, Mehrara B J.
The effect of postoperative anticoagulation on microvascular thrombosis.
Ann Plast Surg.
2007;
59
(1)
36-39, discussion 39–40
MissingFormLabel
- 151
Radomski M W, Palmer R M, Moncada S.
Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium.
Lancet.
1987;
2
(8567)
1057-1058
MissingFormLabel
- 152
Azizzadeh B, Buga G M, Berke G S, Larian B, Ignarro L J, Blackwell K E.
Inhibitors of nitric oxide promote microvascular thrombosis.
Arch Facial Plast Surg.
2003;
5
(1)
31-35
MissingFormLabel
- 153
Miyakis S, Lockshin M D, Atsumi T et al..
International consensus statement on an update of the classification criteria for
definite antiphospholipid syndrome (APS).
J Thromb Haemost.
2006;
4
(2)
295-306
MissingFormLabel
- 154
Cervera R, Piette J C, Font J Euro-Phospholipid Project Group et al.
Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of
disease expression in a cohort of 1,000 patients.
Arthritis Rheum.
2002;
46
(4)
1019-1027
MissingFormLabel
- 155
Espinosa G, Cervera R.
Antiphospholipid syndrome: frequency, main causes and risk factors of mortality.
Nat Rev Rheumatol.
2010;
6
(5)
296-300
MissingFormLabel
- 156
Mehdi A A, Salti I, Uthman I.
Antiphospholipid syndrome: endocrinologic manifestations and organ involvement.
Semin Thromb Hemost.
2011;
37
(1)
49-57
MissingFormLabel
- 157
Cervera R, Asherton R A.
Catastrophic antiphospholipid syndrome.
Pathophysiol Haemost Thromb.
2006;
35
(1-2)
181-186
MissingFormLabel
- 158
Asherson R A, Cervera R, Piette J C et al..
Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients.
Medicine (Baltimore).
1998;
77
(3)
195-207
MissingFormLabel
- 159
Asherson R A, Cervera R, Piette J C et al..
Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of
80 patients.
Medicine (Baltimore).
2001;
80
(6)
355-377
MissingFormLabel
- 160
Cervera R, Khamashta M A, Shoenfeld Y Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies) et al.
Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a
multicentre prospective study of 1000 patients.
Ann Rheum Dis.
2009;
68
(9)
1428-1432
MissingFormLabel
- 161
Bucciarelli S, Erkan D, Espinosa G, Cervera R.
Catastrophic antiphospholipid syndrome: treatment, prognosis, and the risk of relapse.
Clin Rev Allergy Immunol.
2009;
36
(2-3)
80-84
MissingFormLabel
- 162
Stein S C, Smith D H.
Coagulopathy in traumatic brain injury.
Neurocrit Care.
2004;
1
(4)
479-488
MissingFormLabel
- 163
Astrup T.
Assay and content of tissue thromboplastin in different organs.
Thromb Diath Haemorrh.
1965;
14
(3-4)
401-416
MissingFormLabel
- 164
Goodnight S H, Kenoyer G, Rapaport S I, Patch M J, Lee J A, Kurze T.
Defibrination after brain-tissue destruction: A serious complication of head injury.
N Engl J Med.
1974;
290
(19)
1043-1047
MissingFormLabel
- 165
Jacoby R C, Owings J T, Holmes J, Battistella F D, Gosselin R C, Paglieroni T G.
Platelet activation and function after trauma.
J Trauma.
2001;
51
(4)
639-647
MissingFormLabel
- 166
Nekludov M, Antovic J, Bredbacka S, Blombäck M.
Coagulation abnormalities associated with severe isolated traumatic brain injury:
cerebral arterio-venous differences in coagulation and inflammatory markers.
J Neurotrauma.
2007;
24
(1)
174-180
MissingFormLabel
- 167
Dietrich W D.
Morphological manifestations of reperfusion injury in brain.
Ann N Y Acad Sci.
1994;
723
15-24
MissingFormLabel
- 168
Dietrich W D, Alonso O, Halley M.
Early microvascular and neuronal consequences of traumatic brain injury: a light and
electron microscopic study in rats.
J Neurotrauma.
1994;
11
(3)
289-301
MissingFormLabel
- 169
Maeda T, Katayama Y, Kawamata T, Aoyama N, Mori T.
Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion
in the rat: role of platelet activating factor.
Acta Neurochir Suppl (Wien).
1997;
70
102-105
MissingFormLabel
- 170
Stein S C, Graham D I, Chen X H, Smith D H.
Association between intravascular microthrombosis and cerebral ischemia in traumatic
brain injury.
Neurosurgery.
2004;
54
(3)
687-691, discussion 691
MissingFormLabel
- 171
Kaufman H H, Hui K S, Mattson J C et al..
Clinicopathological correlations of disseminated intravascular coagulation in patients
with head injury.
Neurosurgery.
1984;
15
(1)
34-42
MissingFormLabel
- 172
Kushimoto S, Yamamoto Y, Shibata Y, Sato H, Koido Y.
Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency in
patients with severe head injury.
Neurosurgery.
2001;
49
(5)
1084-1089, discussion 1089–1090
MissingFormLabel
- 173
Grenander A, Bredbacka S, Rydvall A et al..
Antithrombin treatment in patients with traumatic brain injury: a pilot study.
J Neurosurg Anesthesiol.
2001;
13
(1)
49-56
MissingFormLabel
- 174
Wahl F, Grosjean-Piot O, Bareyre F, Uzan A, Stutzmann J M.
Enoxaparin reduces brain edema, cerebral lesions, and improves motor and cognitive
impairments induced by a traumatic brain injury in rats.
J Neurotrauma.
2000;
17
(11)
1055-1065
MissingFormLabel
- 175
Dudley R R, Aziz I, Bonnici A et al..
Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight
heparin: risks and benefits.
J Neurotrauma.
2010;
27
(12)
2165-2172
MissingFormLabel
- 176
Roos Y B, de Haan R J, Beenen L F, Groen R J, Albrecht K W, Vermeulen M.
Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a
prospective hospital based cohort study in the Netherlands.
J Neurol Neurosurg Psychiatry.
2000;
68
(3)
337-341
MissingFormLabel
- 177
Vergouwen M D, Vermeulen M, Coert B A, Stroes E S, Roos Y B.
Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation
for delayed cerebral ischemia.
J Cereb Blood Flow Metab.
2008;
28
(11)
1761-1770
MissingFormLabel
- 178
Romano J G, Forteza A M, Concha M et al..
Detection of microemboli by transcranial Doppler ultrasonography in aneurysmal subarachnoid
hemorrhage.
Neurosurgery.
2002;
50
(5)
1026-1030, discussion 1030–1031
MissingFormLabel
- 179
Giller C A, Giller A M, Landreneau F.
Detection of emboli after surgery for intracerebral aneurysms.
Neurosurgery.
1998;
42
(3)
490-493, discussion 493–494
MissingFormLabel
- 180
Crompton M R.
The pathogenesis of cerebral infarction following the rupture of cerebral berry aneurysms.
Brain.
1964;
87
491-510
MissingFormLabel
- 181
Stein S C, Browne K D, Chen X H, Smith D H, Graham D I.
Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy
study.
Neurosurgery.
2006;
59
(4)
781-787, discussion 787–788
MissingFormLabel
- 182
Wurm G, Tomancok B, Nussbaumer K, Adelwöhrer C, Holl K.
Reduction of ischemic sequelae following spontaneous subarachnoid hemorrhage: a double-blind,
randomized comparison of enoxaparin versus placebo.
Clin Neurol Neurosurg.
2004;
106
(2)
97-103
MissingFormLabel
- 183
Roos Y. STAR Study Group .
Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled
trial.
Neurology.
2000;
54
(1)
77-82
MissingFormLabel
- 184
Chwajol M, Starke R M, Kim G H, Mayer S A, Connolly E S.
Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage.
Neurocrit Care.
2008;
8
(3)
418-426
MissingFormLabel
- 185
Starke R M, Kim G H, Fernandez A et al..
Impact of a protocol for acute antifibrinolytic therapy on aneurysm rebleeding after
subarachnoid hemorrhage.
Stroke.
2008;
39
(9)
2617-2621
MissingFormLabel
- 186
Pabinger I, Karnik R, Lechner K, Slany J, Niessner H.
Coumarin induced acral skin necrosis associated with hereditary protein C deficiency.
Blut.
1986;
52
(6)
365-370
MissingFormLabel
- 187
McGehee W G, Klotz T A, Epstein D J, Rapaport S I.
Coumarin necrosis associated with hereditary protein C deficiency.
Ann Intern Med.
1984;
101
(1)
59-60
MissingFormLabel
- 188
Rose V L, Kwaan H C, Williamson K, Hoppensteadt D, Walenga J, Fareed J.
Protein C antigen deficiency and warfarin necrosis.
Am J Clin Pathol.
1986;
86
(5)
653-655
MissingFormLabel
- 189
Sallah S, Abdallah J M, Gagnon G A.
Recurrent warfarin-induced skin necrosis in kindreds with protein S deficiency.
Haemostasis.
1998;
28
(1)
25-30
MissingFormLabel
- 190
Dahlbäck B.
New molecular insights into the genetics of thrombophilia. Resistance to activated
protein C caused by Arg506 to Gln mutation in factor V as a pathogenic risk factor
for venous thrombosis.
Thromb Haemost.
1995;
74
(1)
139-148
MissingFormLabel
- 191
Kiehl R, Hellstern P, Wenzel E.
Hereditary antithrombin III (AT III) deficiency and atypical localization of a coumarin
necrosis.
Thromb Res.
1987;
45
(2)
191-193
MissingFormLabel
- 192
Fluri S, Kaczala G W, Leibundgut K, Alberio L.
Chickenpox is not always benign: postvaricella purpura fulminans requires prompt and
aggressive treatment.
Pediatr Emerg Care.
2010;
26
(12)
932-934
MissingFormLabel
- 193
Sharma V K, Dubey T N, Dave L, Agarwal A.
Postvaricella purpura fulminans with no evidence of disseminated intravascular coagulation
(DIC) or protein S deficiency.
J Indian Med Assoc.
2010;
108
(8)
529-530
MissingFormLabel
- 194
Francis Jr R B.
Acquired purpura fulminans.
Semin Thromb Hemost.
1990;
16
(4)
310-325
MissingFormLabel
- 195
Josephson C, Nuss R, Jacobson L et al..
The varicella-autoantibody syndrome.
Pediatr Res.
2001;
50
(3)
345-352
MissingFormLabel
- 196
Manco-Johnson M J, Nuss R, Key N et al..
Lupus anticoagulant and protein S deficiency in children with postvaricella purpura
fulminans or thrombosis.
J Pediatr.
1996;
128
(3)
319-323
MissingFormLabel
- 197
Busuttil D P, Hay C R, Lewis M A, Wynn R F.
Aggressive multiple modality therapy for varicella-associated purpura fulminans.
Br J Haematol.
2000;
110
(4)
1012-1013
MissingFormLabel
Hau C. KwaanM.D. Ph.D.
Marjorie C. Barnett Professor of Hematology-Oncology, Professor of Medicine, Northwestern
University Feinberg School of Medicine
710 Fairbanks Court, Olson Pavilion, Room 8258, Chicago, IL 60611
Email: h-kwaan@northwestern.edu