Transcription
Another day, another hematology video from Medicos Perfectionist, and my series about bleeding and coagulation disorders. We have been talking about fibrinolysis for several videos. In the previous video, I've told you the clinical uses of TPA. Today, let's talk about this fibrinolytic or thrombolytic therapy with the great streptokinase. It's actually not so great; it's allergic, it has increased risk of bleeding, etc., as well as transient hypotension. So, with that being said about the crazy garbage streptokinase, let's get started. [Music]
This is a sample of my previous videos about bleeding and coagulation, so make sure to subscribe and save this playlist. As you know, hemostasis, the prevention of blood loss, has many steps. We have talked about vasoconstriction before, temporarily, with blood coagulation. Now we're talking fibrinolysis. Plasmin digests fibrin into FDPs, digests fibrinogen into FDPs, digests 5, 8, 2, and 12. If you leave plasmin free all the time, it will degrade every clot, and you will bleed. That's why we need an inactive precursor called plasminogen. We need TPA to activate it into plasmin. Plasmin, the fibrin lysin, comes from plasminogen, pro-fibrin lysin, which is a zymogen, which comes from the liver. When the clot is being formed, plasminogen gets incorporated into the fibrin fibers. Then TPA comes, converts plasminogen to the active plasmin, and creates the fiber into fibrin degradation products, fibrin into fibrin degradation products, the stabilized fibrin into D-dimer.
So here's the whole story of fibrinolysis: first, let's form the clot; intrinsic and the extrinsic coagulation pathways, prothrombinase complex, activate prothrombin, thrombin, fibrinogen into fibrin. Plasminogen is getting incorporated within the fibrin fibers, together with TPA. TPA will activate plasminogen to plasmin. This process takes days. Plasmin will degrade fibrin into fibrin degradation products, degrade fibrinogen into fibrin degradation products, and will degrade the stabilized fibrin into the D-dimer. Not only that, it will digest 5, 8, 2, and 12. Plasmin is a bad bastard.
Two types of plasminogen activators: the tissue type plasminogen activator and the urokinase type plasminogen activator, TPA, UPA. We find TPA from the endothelium, which types the injured endothelium, and UPA was first discovered in the human urine. Maybe you can urinate on a clot to break it down—who knows? I'm just a stupid idiot. Plasminogen and TPA, they get incorporated into fibrin, forming a ternary complex, which will help in plasminogen activation into plasmin. If you want to learn more about hematology, I have 50 hematology cases, many of them are really difficult; they are available on patreon.com/medicosis. Enough said. You know that we have TPA, UPA, we have the recombinant TPA or rtPA, we have the streptokinase coming from the bacteria. So streptokinase comes from bacteria; it's less effective, and we talked about it—oh, we're talking about it right now—a N-acetylated plasminogen streptokinase activator complex. So it's the streptokinase coupled to the plasminogen. Then we have the recombinant guys: alteplase, reteplase, tenecteplase.
Clinical uses of TPA and all of these crazy drugs, clot policing drugs, thrombolytics, fibrinolytics, or clot busters: we have acute MI, strokes, DVT, and PE. Never used in hemorrhagic strokes, only in ischemic. How do you tell the difference between ischemic and hemorrhagic strokes? CT scan of the head without contrast. Here are the clinical uses of TPA: coronary artery occlusion, the acute MI, ischemic strokes only—the ischemic, not the hemorrhagic; pulmonary embolism. Don't forget the earlier the better; time is money. And catheter-induced chemical thrombolysis of the clot: poke baby, poke the clot and add chemical to the catheter, the chemical being TPA or the urokinase. So we can use it to open the blocked coronary artery, that's the cause of the low output cardiac failure, what the layman calls it: cardiogenic shock. And we can use TPA in paroxysmal nocturnal hemoglobinuria patients because they are more prone to thrombosis.
Stroke is divided into ischemic stroke, hemorrhagic stroke, due to occlusion of an artery, due to a bleeding artery. How to tell the difference? Head CT scan without contrast. Ischemic stroke is divided into focal and global. The focal TIA, an ischemic stroke, ischemic stroke, thrombotic, embolic, and lacunar. What's the most common use of TPA or streptokinase? Ischemic strokes. Too little TPA, and you will clot; too much TPA, and you will bleed. When you have too much TPA, we call this the systemic lytic state; you are breaking down clots all over your body, till you bleed to death. Talked about this slide in the previous video, but repetition is the mother of pedagogy. Two types of plasminogen: we have that's local, that's incorporated to the fibrin, and then we have the plasminogen that's circulating freely in the plasma. Cool. When you activate the plasminogen incorporated, it gives you localized fibrinolysis; it breaks down the fibrin and only at that location, which is good, which is desirable, which is useful. On the other hand, when you activate this plasminogen, you end up with systemic lytic state; you are destroying fibrin fibers all over the body, including the useful, benign clots that you have when you like hurt yourself in a minor trauma or something. This increases the risk of bleeding; that's why systemic lytic state is crazy. Who activates this plasminogen? TPA or streptokinase or l2-plasase or whatever. Who activates this again? TPA.
So TPA drugs have two different subtypes: fibrin-specific plasminogen activators, which is the superior class—alteplase, reteplase, tenecteplase—and fibrin nonspecific plasminogen activator. They activate plasminogen all over the body. Streptokinase: garbage, and it's replaced garbage. Urokinase: garbage. I'm not saying garbage, of course; they are better than nothing; they are better than leaving the patient to clot and die, but they are inferior to those great guys. Alteplase, reteplase, tenecteplase, why? Because these guys are fibrin-specific; they only activate the plasminogen that's incorporated within the fibrin fibers; they will only bust this clot and not any other. So streptokinase, not an enzyme, cannot directly activate plasminogen to plasmin. Instead, it forms a complex with plasminogen; this yields a conformational change into the plasminogen. Plasminogen now is accessible; the active site is exposed. So this complex now activates plasminogen into plasmin. Plasmin degrades fibrinogen and fibrin and stabilized fibrin. This complex is fibrin nonspecific; it's one of the ugly class, the inferior class. So it activates both the plasminogen which incorporated in the fibrin, as fibrin-bound plasminogen. This will yield a localized fibrinolysis, which is good. Also, it will activate the circulating plasminogen into plasmin. This is called systemic lytic state; increased the risk of bleeding, which is horrible. That's why streptokinase is inferior to alteplase, for example.
Now let's talk about side effects: allergic reaction, big time—5% of patients; transient hypotension, and I will tell you why. Then, if the patient can develop antibodies against streptokinase, leading to decreased effectiveness. Patients with prior streptococcal infection may develop antibodies against streptokinase, again decreasing effectiveness. Streptokinase is not that great after all. Streptokinase is administered via intravenous infusion. There is a difference between intravenous injection and intravenous infusion. Intravenous injection takes, I don't know, like ten seconds, depending on the nurse; if you have a crazy nurse, it can take two seconds. But intravenous infusion is a slow process, slow cooker, over 30 to 60 minutes. So, in case of myocardial infarction, when we say intravenous infusion, we infuse streptokinase into the vein, and streptokinase now is acting as TPA, activates plasminogen to plasmin to destroy the clot. Intravenous infusion.
So why do we get transient hypotension after streptokinase administration? Let's talk about the high molecular weight kininogen. Welcome back; we missed you. Thanks to collect rain. We have bradykinin. But I didn't tell you that plasmin can also activate high molecular weight kininogen into bradykinin. What will bradykinin do? Bronchoconstriction, and cough, the increased visibility, and angioedema, increased pain, increased vasodilation, and natural races, leading to hypotension. So transient hypotension after streptokinase administration is bradykinin-induced. Streptokinase is highly, highly antigenic, which means allergic reactions are common. The patient had taken streptokinase in the last six months? Do not, do not give streptokinase again. But it's like three months ago? I don't care; you can get an allergic reaction, which is never fun. It's an absolute contraindication if you have a patient who has streptokinase in the last six months. By the way, that's a very unfortunate patient that needs streptokinase twice in a six-month period.
Okay, let's say you have a patient with acute myocardial infarction and you like to use lytic therapy. The most effective method is an anticoagulant such as heparin plus a fibrinolytic such as TPA. Streptokinase; add them together; two are better than one. But don't forget that percutaneous coronary intervention is superior to TPA, big time. But if we're talking TPA, you better give it with heparin, baby. Why not warfarin? That's a very good question, because warfarin is very slow, very slow, like heavy heart of heparin bridging. Warfarin is very slow, man; it has to go to the liver, and then order the liver to begin carboxylation, which needs vitamin K to stop producing the vitamin K dependent coagulation factors, which are prothrombin, seven, nine, ten, protein C, and protein S. So the more of the story, warfarin takes time. You give heparin because it's an acute myocardial infarction, you stupid idiot.
The know-crazy generation and its replacement, which is also one of the inferior clients. We get streptokinase just at plasminogen and an acyl group; single bolus infusion. This is more convenient to administer than streptokinase. Remember, streptokinase is administered via IV infusion, which takes half an hour to one hour. This is just a single bolus infusion, so the nurse can like go texting and go eat her lunch again. Fibrin nonspecific plasminogen activator; it's nonspecific; it's one of the garbage group; it will cause systemic lytic state, increased risk of bleeding; allergic reaction, transient hypotension are also possible. So the only thing that's good about n-streptokinase is single bolus infusion. Thank you so much, guys, for watching. Don't forget to subscribe, follow me on Facebook and Instagram, get my notes, get my cases by going to patreon.com/medicosis, and I'll send you my bloody Dropbox links. Thank you for watching; be safe, stay happy, and study hard. This is Medicos Perfectionist; elsewhere medicine makes perfect sense.