COAGULATION CASCADE
COAGULATION DISORDERS
All cause deep tissue bleeding, joint bleeding and post-surgical bleeding. These patients can form platelet plugs (normal bleeding times), but the plug washes away soon after it forms. The patient will seem fine at the end of a procedure, but an hour or so later will hemorrhage profusely.
HEMOPHILIA A - a genetic X-linked Recessive condition affecting Factor 8 (A sounds like Eight). Elevated PTT and normal INR.
HEMOPHILIA B - same as Hemophilia A, but it affects Factor 9
HEMOPHILIA C - same as Hemophilia A, but it affects Factor 11
VITAMIN K DEFICIENCY - disrupts factors 7, C, 9, S, 10 and 2 (ordered here from shortest to longest half lives). Vitamin K is acquired by the diet and microbiome, and activated by Epoxide Reductase in the liver (which Warfarin blocks). Since babies / people-on-long-term-antibiotics don’t have gut floras, they need Vitamin K supplements. Inject every baby with Vitamin K. Vitamin K is fat soluble, so someone with fat malabsorption will be deficient. The PT and PTT are elevated. The bleeding time is normal.
LIVER DISEASE - the coag factors are made in the liver, and the liver has Epoxide Reductase which turns on Vitamin K. People with cirrhosis typically have a hard time stopping big internal bleeds, the best example being a variceal bleed.
HEPARIN INDUCED THROMBOCYTOPENIA
Heparin-Induced Thrombocytopenia (HIT) is a rare autoimmune side effect of Heparin. It’s really easy to spot -- when a patient started on Heparin paradoxically starts to clot. What happens is that the Heparin likes to hang out on the surface of platelets, bound to a surface protein called Platelet Factor 4. Bound together, those two molecules look mighty suspicious to the immune system. The body pumps out IgG molecules trained to destroy the Heparin-PF4 duo. When the IgG binds, this triple-molecule-complex weirdly activates platelets. The platelets degranulate and clot (symptoms). Much more common with Unfractionated Heparin than Low Molecular Weight Heparin. Stop the Heparin, and then give a Direct Thrombin Inhibitor like Argatroban or Bivalirudin.
DISSEMINATED INTRAVASCULAR COAGULATION
DIC
DIC is the baddest of the bleeding disorders. It’s a complete breakdown of the clotting process. During really serious illnesses where there is widespread inflammation (like sepsis), often the inflammation damages the blood vessels. The body tries to plug up the hurt vessels. Your body has over 60,000 miles of blood vessels, so A LOT of clotting factors can be consumed. And whenever a hole isn’t patched, the subendothelium is exposed, and you definitely don’t want that. The subendothelium is full of pro-clotting proteins, and if enough of them are dumped into circulation, then huge blood clots can form and damage your organs. So in summary, all of the clotting factors are used up in a short time, and harmful clots form. You’re bleeding and clotting simultaneously! Often the first sign of DIC is bleeding at IV sites. It will be followed by rectal, lung and mucosal bleeding, and then by end organ failure.
There are two classic types of DIC patients. One is a very sick person in the ICU, who develops DIC a few days after admission. The second is a mother undergoing a complicated delivery. Some other conditions are strongly tied to DIC: Sepsis, Pancreatitis, Adenocarcinoma, AML (Promyelocytic variety), and Rattlesnake bites.
DIC is fairly straightforward to recognize on the basis of labwork. Every component of the coagulation panel will be abnormal. Seriously, all of them! There will be low platelets, high PT, high PTT, prolonged bleeding time, low fibrinogen and elevated D-dimer.
DIC has a high mortality rate. The treatment is twofold. First, fix the cause (in the case of sepsis, give antibiotics). Second, transfuse them with Fresh Frozen Plasma to try and normalize their coagulation cascade.
HYPERCOAGULATION DISORDERS
These are all Autosomal Dominant genetic conditions. A patient with one of these conditions will develop multiple DVTs and PEs at an early age. They’re more likely to have miscarriages. Venous clots will sometimes even occur in unusual places, like the hepatic vein or dural sinus.
FACTOR V LEIDEN - condition with a dysfunctional Factor 5, making it invincible to Protein C. The patient clots a little bit more. Like 5% of white people have this, so suspect FVL in any young white person who gets multiple blood clots (and don’t have any other clotting risk factors like smoking or birth control pills).
ANTITHROMBIN DEFICIENCY - ASYMPTOMATIC 90% of the time. Recall that Heparin works by making Antithrombin (aka Antithrombin III) a thousand times more effective at blocking 2a and 10a. So patients with Antithrombin Deficiency don’t get much of an effect from Heparin. You can acquire this condition if you pee out too much of your Antithrombin (nephrotic syndrome). Low yield.
PROTEIN C & S DEFICIENCY - These two proteins are our bodies own homegrown anticoagulants! Protein C has a short half-life (6 hours). When these patients are placed on Warfarin, Protein C activity falls to zero in 6 hours, causing a temporary paradoxical hypercoagulable state because of the increased activity of Factors 5 and 8. This causes hemorrhagic skin necrosis, a side effect not commonly seen in normal people.
