Read on Twitter
So I was hoping to avoid a COVID heme #tweetorial but with >50% of the votes on my survey, the people have spoken.
(but hold on, this is going to be a long one)
Coagulopathy in patients with COVID-19 is increasingly described. Some argue that it is akin to DIC...
1/n
(but hold on, this is going to be a long one)
Coagulopathy in patients with COVID-19 is increasingly described. Some argue that it is akin to DIC...
1/n
While others argue it is simply a hypercoagulable state 2/2
inflammation. The link btw thrombosis and inflammation is well described and COVID continues to add support to this phenomenon.
One of the first pieces of evidence to support DIC comes from Tang et al (Wuhan).
2/n
inflammation. The link btw thrombosis and inflammation is well described and COVID continues to add support to this phenomenon. One of the first pieces of evidence to support DIC comes from Tang et al (Wuhan).
2/n
Out of 183 COVID patients, lab criteria for DIC were met in 71.4% of non-survivors versus 0.6% in survivors.
A progressivein PT and D-dimer was seen in the 7 days following admission in non-survivors. A similar pattern (but only D-dimer) was seen in Ireland. @Jme_os
3/n
A progressive
in PT and D-dimer was seen in the 7 days following admission in non-survivors. A similar pattern (but only D-dimer) was seen in Ireland. @Jme_os 3/n
Another study of 199 patients found that D-dimer >1ug/ml was associated with an adjusted hazard ratio of 18.4 for in-hospital mortality.
For this reason ISTH guidelines recommend hospitalization in patients with 3-4x D-dimer regardless of other criteria!
4/n
For this reason ISTH guidelines recommend hospitalization in patients with 3-4x
D-dimer regardless of other criteria! 4/n
Interestingly, clinical bleeding has not been commonly seen. Given this, Marongiu et al hypothesize that rather than overt DIC,D-dimer is a marker of pulmonary vascular thrombosis and subsequent activation of fibrinolysis. A local DIC! (is that an oxymoron?)
5/n
D-dimer is a marker of pulmonary vascular thrombosis and subsequent activation of fibrinolysis. A local DIC! (is that an oxymoron?) 5/n
Other lab abnormalities includefibrinogen, VWF andFVIII ( 
PTT) This is important when it comes to anticoagulation (AC) as following PTT will lead to heparin doses and risk for bleeding. Anti-Xa monitoring (as always, in my opinion) is a better option.
6/n
fibrinogen, VWF andFVIII ( PTT) This is important when it comes to anticoagulation (AC) as following PTT will lead to heparin doses and risk for bleeding. Anti-Xa monitoring (as always, in my opinion) is a better option. 6/n
TEG studies out of Italy have demonstrated severe hypercoagulability hypothesized to be 2/2fibrinogen as well as polymerization.
It is no surprise then that COVID-19 has been shown to result in anrisk of thrombosis.
7/n
fibrinogen as well as polymerization. It is no surprise then that COVID-19 has been shown to result in an
risk of thrombosis. 7/n
When interpreting VTE data on COVID it is important to appreciate differences in underlying risk btw populations.
At baseline, Chinese people have a 3-4x lower VTE risk than Caucasians and are less likely to be started on prophylactic AC.
8/n
At baseline, Chinese people have a 3-4x lower VTE risk than Caucasians and are less likely to be started on prophylactic AC.
8/n
Also important to acknowledge difficulty in diagnosis.D-dimers-nonspecific. Prone patients may not be able to undergo imaging. Hospitals may avoid CT scans toinfectious risk. Obi et al( @GBarnesMD) nicely summarized @umichmedicine approach to dx. ( …https://www-sciencedirect-com.proxy.lib.umich.edu/science/article/pii/S2213333X20302213?via%3Dihub)
9/n
D-dimers-nonspecific. Prone patients may not be able to undergo imaging. Hospitals may avoid CT scans toinfectious risk. Obi et al( @GBarnesMD) nicely summarized @umichmedicine approach to dx. ( …https://www-sciencedirect-com.proxy.lib.umich.edu/science/article/pii/S2213333X20302213?via%3Dihub)9/n
Sick patients are at risk for thrombosis 2/2 many factors (premorbid medical issues, prolonged immobility, invasive tests, indwelling catheters, renal dysfunction, and often infection/inflammation).
But rate of thrombosis in COVID seems to be significantly higher.
10/n.
But rate of thrombosis in COVID seems to be significantly higher.
10/n.
risk is likely due to excessive inflammation, platelet activation, endothelial dysfunction, in addition to those listed above.A Chinese study w/81 COVID ICU patients found VTE in 25%. Notably, none received AC (whereas prophy (ppx)AC would be typical in ICU in US)
11/n
A Dutch study of 184 patients receiving prophylactic AC found VTE in 27% (PE most common at 80%).
A French study of 26 patients found VTE in 69% of patients on therapeutic (56%) or prophylactic (100%) AC.
The typical failure rate of AC ppx in the ICU is 7.7%.
12/n
A French study of 26 patients found VTE in 69% of patients on therapeutic (56%) or prophylactic (100%) AC.
The typical failure rate of AC ppx in the ICU is 7.7%.
12/n
Postmortem path has confirmed PE, as well as disseminated microthrombi and hemorrhagic necrosis.
The ACE2 receptor is found on pneumocytes, and vascular endothelial cells (EC). As such, some pathology may be secondary to direct EC injury, activation, and damage.
13/n
The ACE2 receptor is found on pneumocytes, and vascular endothelial cells (EC). As such, some pathology may be secondary to direct EC injury, activation, and damage.
13/n
Another component is hypofibrinolysis (lack of appropriate clot break) Fibrin deposition in air space and parenchyma is seen in ARDS.
TF is exposed on damaged alveolar endothelium and leukocytesfibrin deposition. PAI-1 (an important inhibitor of fibrinolysis)
14/n
) Fibrin deposition in air space and parenchyma is seen in ARDS. TF is exposed on damaged alveolar endothelium and leukocytes
fibrin deposition. PAI-1 (an important inhibitor of fibrinolysis)14/n
from lung epithelium and ECs (release promoted by CRP) hypofibrinolysis. Platelet infiltration may result in local PAI-1 release. Other inhibitors also(TAFI), but PAI-1 promising as biomarker as one study found levels >640 to be 100% predictive of mortality. 15/n
Overexpression overcomes uPA,tPA. Given success in ARDS, tPA has been tried in a number of COVID pts.
There is evidence that AC is helpful, at least in high risk pts. In a study of 449 pts (22% rcved AC), 28d mortality
w/ AC in pts w/ SIC≥4 or D-dimer > 6xULN.
16/n
There is evidence that AC is helpful, at least in high risk pts. In a study of 449 pts (22% rcved AC), 28d mortality
w/ AC in pts w/ SIC≥4 or D-dimer > 6xULN.16/n
ISTH guidelines recommend ppx LMWH but Barrett et al argue this isn’t enough. They recommend systemic AC with UFH. Why?
Fibrinogen >700 confers AC resistance. At >900, there is 3Xin blood viscosity at low shear (completing Virchow's triad!
17/n
Fibrinogen >700 confers AC resistance. At >900, there is 3X
in blood viscosity at low shear (completing Virchow's triad!17/n
Heparin may provide added benefit as in vivo studies of coronavirus infection demonstrate that endogenous heparan sulfate aids viral entry into host cell.
UFH may function as decoy receptor/sink toinfectivity and clearance.
18/n
UFH may function as decoy receptor/sink to
infectivity and clearance.18/n
Many were surprised by ISTH transfusion guidelines, esp keeping fibrinogen >2g in non-bleeding pts. Givenrisk of VTE, and current blood supply issues, this doesn't seem well considered. Akima et al ( @IsthPresident @bhwords ) also questioned this recommendation..
19/n
risk of VTE, and current blood supply issues, this doesn't seem well considered. Akima et al ( @IsthPresident @bhwords ) also questioned this recommendation.. 19/n
along with recommendation for admission forD-dimers. They also propose that coagulopathy could be all 2/2 sepsis induced hepatopathy ( @ebtapper)!
There is a lot to learn, and many questions remain unanswered.
But isn't hematology (especially hemostasis) amazing?!
20/fin
D-dimers. They also propose that coagulopathy could be all 2/2 sepsis induced hepatopathy ( @ebtapper)! There is a lot to learn, and many questions remain unanswered.
But isn't hematology (especially hemostasis) amazing?!
20/fin
